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December 2008

Structure & Symmetry

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ORG-041-GFPTaggedAd_ASBMB_v7.indd 1 10/20/08 12:29:39 PM contents December 2008 On the Cover: Captivated by the symmetry society news of molecular structure, Sung-Hou Kim has been a 2 From the Editor leader in revealing symmetry 3 President’s Message through his studies in crystallography and 5 Letters to the Editor structural genomics. 30 6 Washington Update 12 Retrospective: Anthony G. San Pietro FASEB releases new Breakthroughs in special interest Bioscience. 6 13 Science’s Role in Foreign Policy 14 ASBMB Round Table: Jim Wells and Mary Woolley 16 Keeping Women in Science 19 Grammar and Writing Tips

2009 meeting 20 The 2009 Fritz Lipmann Lectureship: Douglas C. Rees 21 The 2009 ASBMB Merck Award: 22 The 2009 FASEB Excellence in Science Award: science focus 30 Sung-Hou Kim: Consummate Crystallographer departments 7 News from the Hill 10 Member Spotlight 23 Education and Training A leaky pipeline for women scientists. 26 Minority Affairs 16 28 BioBits resources 34 Career Opportunities podcast summary 36 Calendar Check out this month’s podcast where we talk with contributors to the upcoming JBC Thematic Minireview Series on Alzheimer Disease. For this and other ASBMB AudioPhiles podcasts go to: www.asbmb.org/audio.aspx

December 2008 ASBMB Today 1 from the editor A monthly publication of The American Society for Biochemistry and Molecular Biology A Year of ASBMB Today Officers By Nicole Kresge Gregory A. Petsko President Heidi E. Hamm Past President Mark A. Lemmon Secretary Merle S. Olson Treasurer s this year winds down and the holiday season sets upon us, I can’t help Council Members Abut reflect upon what a momentous year 2008 has been for ASBMB Dafna Bar-Sagi Alan Hall John D. Scott Today. We’ve run stories on everything from Carolyn Bertozzi’s innovations in Joan A. Steitz Ann M. Stock Kevin Struhl James A. Wells Adrian Whitty glycobiology (February 2008) and a tax primer for postdoctoral fellows (March Ex-Officio Members 2008) to a summary of where Presidential candidates John McCain and Barack Ellis Bell Obama stand on issues related to biomedical research (October 2008). This Chair, Education and Professional Development Committee year marked the debut of a new series of articles called ScienCentric, which Laurie S. Kaguni Chair, Meetings Committee featured the Rutgers Center for Lipid Research (May 2008) and Cornell’s John D. Scott Weill Institute for Cell and Molecular Biology (September 2008), and we also Chair, Membership Committee George Hill started up a new column called Sci.Comm (September 2008), which covers the Chair, Minority Affairs Committee intersection between science communication and communication technology. Joan W. Conaway James H. Hurley And finally, we launched an ASBMB Today Round Table series by interviewing Co-chairs, 2009 Program Committee Nobel laureate and political activist Peter Agre (October 2008). Ralph A. Bradshaw Chair, Public Affairs Advisory Committee 2008 also marked a huge step for ASBMB Today in the electronic world. In Toni M. Antalis Chair, Publications Committee January, we unveiled the launch of our new digital magazine—an interactive, Herbert Tabor vivid replica of the print edition which offers our readers an experience very Editor, JBC Ralph A. Bradshaw much like an ink-and-paper magazine delivered electronically. Using this A. L. Burlingame platform, we were able to include online-only features in the magazine, such Co-editors, MCP Edward A. Dennis as a video centerfold featuring movies from presentations at the 2008 annual Joseph L. Witztum meeting (June 2008) and a slide show of Cornell’s Weill Institute for Cell and Co-editors, JLR Molecular Biology (September 2008). We were also able to provide ASBMB ASBMB Today Editorial Advisory Board Alex Toker Today readers with pop-up links to podcasts related to specific articles, such Chair as a chat with MCP Editorial Board Member Robert Chalkley about his trip Greg P. Bertenshaw Craig E. Cameron A. Stephen Dahms Irwin Fridovich to the World HUPO meeting in Amsterdam (November 2008). Jonathan Gitlin richard W. Hanson And finally, we won a 2008 APEX Award for Publication Excellence in the Elizabeth A. Komives Bettie Sue Masters Luke A. O’Neill Duanqing Pei category of Most Improved Magazines and Journals. Carol C. Shoulders robert D. Wells In 2009, we intend to continue improving both the digital and print ASBMB Today magazine. We’ll take further advantage of the digital platform, offering more Nicole Kresge Editor [email protected] podcasts, videos, slide shows, and perhaps even Nick Zagorski Science Writer some web chats. We also hope to improve [email protected] the content of our magazine, adding Nancy J. Rodnan Director of Publications [email protected] more articles that cater to our readers’ Barbara Gordon Executive Director interests. As always, we appreciate [email protected] any suggestions or comments from Magazine design & production: Amy Phifer our readers, so please send them For information on advertising contact to [email protected]. Capitol Media Solutions at 800-517-0610 or [email protected] Happy Holidays!

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2 ASBMB Today December 2008 president’smessage First Impressions, Second Chances By Gregory A Petsko

y now most of you have probably heard at least 2) Design Implementation Bsomething about the reforms to the peer review Phase system that the National Institutes of Health (NIH) is in In March 2008, Zerhouni estab- the process of implementing. I’ve been interested in this lished the Steering Committee Peer Review Implemen- topic for many years and have written extensively about tation Group to draft implementation plans for each the troubles peer review was going through because of recommendation in the Phase 1 report. The committee the funding crunch. I also proposed a set of changes to convened subgroups led by Berg, Tabak, and Story Lan- the process, and I’m delighted to see that the committees dis, Director of the National Institute of Neurological that recommended the new peer review guidelines seem Disorders and Stroke (NINDS). Subgroup membership to have reached many of the same conclusions that I did. consisted of NIH program and review officers, planning But one item in particular that I considered recom- and evaluation experts, and statisticians. Feedback was mending but decided against after long deliberation is a solicited from both NIH internal and external commu- major feature in the new process. It’s worth going over nities. This feedback, together with careful consideration the way these reforms were developed, because it will of the pros and cons of both individual and combined help explain why I think that one of them in particular recommendations, was what led to the final decisions deserves rethinking. on enhancements—that’s the word NIH uses; apparently The assessment of peer review has been going on they’re nervous about calling them reforms—to the peer for over a year now. In June 2007, Elias Zerhouni, then review system. NIH Director, initiated the effort to formally review the On June 6, 2008, Zerhouni announced the Peer NIH peer review system. External and internal work- Review Enhancements and Implementation Plan (see ing groups, with input from both internal and external the press release at tinyurl.com/6ddu2t), and Tabak communities, considered all aspects of the reviewing presented the Implementation Plan to the Advisory process. The year-long effort, which resulted in selected Committee to the Director (ACD). recommendations, included the following phases. 3) Implementation Phase 1) Diagnostic Phase In July 2008, Zerhouni established a Peer Review Over- The diagnostic phase involved an in-depth evaluation sight Committee (PROC)—I know, I know, we ought to of the current NIH peer review system. In June 2007, declare this an acronym-free column, but believe me, if Zerhouni established two working groups: Externally, you deal with Washington, this is the way you have to the Advisory Committee to the Director Working write to initiate implementation. The PROC, chaired by Group (ACD WG), co-chaired by Keith Yamamoto of NIH Deputy Director Raynard Kington, who has just the University of California, San Francisco, and Law- been appointed acting director following the resigna- rence Tabak, Director of the NIH National Institute tion of Zerhouni, established subgroups consisting of of Dental and Craniofacial Research (NIDCR); and NIH program, review, grants management, and evalu- Internally, the Steering Committee Working Group (SC ation staff to assist with the implementation effort. On WG), co-chaired by Tabak and Jeremy Berg, Director of Sept. 12, 2008, the PROC and subgroup chairs presented the NIH National Institute of General Medical Sciences to Zerhouni the first of the preliminary implementa- (NIGMS). The working groups solicited formal input tion plans for the 2009 through 2010 calendar years. from key stakeholders before releasing the Final Draft Although specific details of the Implementation Plans Report on Feb. 29, 2008, which documented the out- continue to be worked through, the first of the prelimi- come of the diagnostic phase and described a prelimi- nary Implementation Plans for the 2009-2010 calendar nary set of recommendations. years are as follows.

December 2008 ASBMB Today 3 presidents message continued Priority Area 1—Engage the Best Reviewers And now, last but certainly not least, the recommenda- • Improve Reviewer Retention: In 2009, new reviewers will tion that I didn’t make and that I think should be thought be given additional flexibility regarding their tour of duty, about some more before implementation: and other efforts will be undertaken to improve retention • New NIH Policy to Fund Meritorious Science Earlier: To of standing review members. ensure that the largest number of high quality and merito- • Recruit the Best Reviewers: A tool kit, incorporating best rious applications receive funding earlier and to improve practices for recruiting reviewers, will be made available system efficiency, NIH will enhance success rates of new to all ICs in 2009. and resubmitted applications by decreasing the number of • Enhance Reviewer Training: In Spring 2009, training will allowed grant application resubmissions (amendments) be available to reviewers and SROs related to the changes from two to one. in peer review. That’s right, from now on, if this is implemented, you • Allow Flexibility through Virtual Reviews: Pilots will be will only get one chance to resubmit a proposal that was conducted in 2009 on the feasibility of using high-band- turned down for funding. If it is turned down a second width support for review meetings to provide reviewers time, you must completely rewrite it—it has to be a new with greater flexibility and alternatives for in-person grant, essentially—if you are going to try to get the same meetings. (I didn’t recommend this, because I have always broad research funded. hated phone conferences, but having done a few recently I think there are several problems with this. First of I have to admit that the web-based, phone-linked review all, it treats all rejections as equal, and they’re not. A grant meetings work better than I thought.) that has been triaged is very different from a grant that just Priority Area 2—Improve the Quality missed being funded. I could see a case for not allowing and Transparency of Review further resubmissions if the first resubmission was tri- • Provide Scores for Streamlined Applications: In 2009, aged. (NIH calls it “streamlined.” But dead is dead in any streamlined applications will receive a preliminary score, language.) A grant that had a respectable score, it seems unlike in the present system. to me, is a victim of tight funding or the whim of one or • Shorten and Restructure Applications: Shorter (12-page two panelists, and it usually represents quite worthwhile research plan) R01 applications (with other activity codes science. To force the PI for such a proposal to rewrite it scaled appropriately) will be restructured to align with completely strikes me as draconian, to say the least. review criteria for January 2010 receipt dates. The pur- Yes, I know the intent here is to make things easier pose of this is to deemphasize the details of how research for the reviewers by trying to hold down the number of is to be carried out, and focus instead on the importance applications, but do you really think it’s going to do that? of the problem being investigated and the track record of It’ll make more work for the submitters, that’s for sure, but the investigator(s). This was one of my major recommen- my guess is that most of them will just keep rewriting and dations, and I’m delighted to see the committee come to submitting because, really, what else can they do? And it’s the same conclusion. It’s possible to nitpick any proposal to death based on real or perceived imperfections in the even possible, the Law of Unintended Consequences being research plan, and I hope there will be less of that now. what it is, that they will actually submit MORE grants, if they think their chances of getting any one funded have Priority Area 3—Ensure Balanced and Fair gone down as a result of this rule. Reviews across Scientific Fields and Career Stages, and Reduce Administrative Burden The National Science Foundation (NSF), which is often more sensible about the whole grants business than NIH, • Review Like Applications Together: In September 2008, has a simpler system. They just treat every proposal as a NIH modified the NIH New Investigator Policy to iden- new submission. Each application is judged on its own tify Early Stage Investigators. In 2009, where possible, merits, and previous reviews are not considered. They tell NIH will cluster new investigator applications (including Early Stage Investigators) for review. The same approach me this works quite well. I understand that the NIH folks will be used for clinical research applications. This considered this alternative but rejected it. Frankly, I can’t recommendation has received some scrutiny. There are a see why. number of people in our Society and in FASEB who are But OK, if they’re going to limit the number of times a concerned about how this will work in practice and what grant can be resubmitted, I think they are making a huge the unintended consequences might be. I’m cautiously mistake if they don’t cut beginning investigators some in favor of trying it out, but I wouldn’t rule out some slack. Learning how to write good grants often takes quite detailed comment from the ASBMB and other societies a bit of time, and a number of rounds of feedback. Again, that might lead to reconsideration. continued at the bottom of page 5

4 ASBMB Today December 2008 letters to the editor

suppose I do, and for that I apologize. deal with a world that no longer exists.” Gene-Xer’s I do not mean to generalize as there is However inspiring this sounds, Hoffer’s fantastic work being done by some of philosophy is not the best formula for Making an the “big” labs. However, it is a sad fact, success in this impact factor-driven Impact but a consensus amongst many of us environment, where we all too often Gene-Xer’s, that we and our gradu- have to deal with learned grant applica- To the Editor: ate students spend a disproportion- tion and journal reviewers who appar- Thank you, Dr. Petsko, for the ate amount of time (and hard-gained ently fear the evolution of concepts and wonderful exposé on impact factors operating funds!) wading through a who choose to ascribe to the comfort- (ASBMB Today, October, 2008). Per- literature that is quite often flawed ing ostrich-head-in-the-sand, “What, haps you might consider commenting (or perhaps simply over-interpreted me worry?” mind-frame championed on Jorge Hirsch’s H-index that meas- because of pressure to publish? I mean, by that other notable philosopher of the th ures a researcher’s impact on science, really! Why are there researchers who 20 century, Alfred E. Neuman. potentially a more appropriate indicator still adhere to the misguided notion Darrell D. Mousseau, Ph.D. of one’s impact in their specific field. that cell signalling cascades are linear?). Cell Signalling Laboratory As a Generation X researcher, I find Of course, the biggest challenge is in University of Saskatchewan myself in the exciting category of scien- convincing journal editors and review- Canada tists who are actually bridging the gap ers (with much tongue-biting, but great between the and its secret, and diplomacy, I might add!) that our data and the interpretation thereof, is indeed Tell Us What You Think the “established” researchers. Unfor- We appreciate receiving letters that are tunately, it is from this pool of “estab- correct. Geographical and institu- suitable for publication regarding issues of lished” researchers, many of whom tional bias renders this an even greater importance or comment on articles appearing wouldn’t know the difference between challenge; I am from the University in ASBMB Today. Letters should be sent to the a restriction site and short sight (but of Saskatchewan. Did I hear you say editor at the address found in the masthead. “Saskatchewhere”? Letters must be signed and must contain the who still contribute as co-authors to writer’s addresss and telephone number. Gene-Xer’s tend to live by Eric Hof- an impossible number of articles each The editor reserves the right to edit all letters year), that high-impact journals all fer’s adage, “In times of change learners for clarity and length. Opinions expressed in too often draw from to review our inherit the earth; while the learned letters do not necessarily reflect ASBMB policy. manuscripts. Do I sound cynical? I find themselves beautifully equipped to

continued from on page 4 about (they are, after all, the lifeblood of our profession), is unless the second resubmission is triaged, I think investiga- not to pay attention to rumors about queuing, which might tors who have never had an NIH grant should be given the make you think you should just get in line with an imper- option of a third resubmission. If study sections do their fect proposal and try to fix it in the first revision. Person- jobs, the additional CONSTRUCTIVE criticism should be ally, I’ve not seen much evidence for queuing in the way very valuable to a young scientist. proposals are ranked, at least in the study sections that I Do you have a different opinion? Good, then let NIH participate in. And if NIH is not going to make allowances know about it. If we want things to improve, we all need to for beginning investigators and sticks with the one resub- take an interest in what is happening. Because the fund- mission-only policy across the board, it’s important that the ing situation is not going to get much better any time first submission be as close to fundable as possible. Besides, soon—I think the recession we’re already in is going to be I think a young investigator should make the strongest case deep and dark compared with the last few—it is imperative he or she can, by writing the best possible proposal, so that that peer review, the jewel in the crown of American sci- the study section has the best possible impression of them ence, works as well as possible. the first time it encounters them. Second chances are all Meanwhile, I think the best advice to give young scien- well and good, but as my mother was fond of saying: “You tists, who are the ones we all need to be most concerned never get a second chance to make a first impression.”

December 2008 ASBMB Today 5 washington update FASEB FASEB Releases Neural Prosthetics Publication BY CARRIE WOLINETZ

ASEB recently announced the on biomaterials, for publication in Frelease of the publication “Build- early 2009. Suggestions for topics ing Electronic Bridges to Bionics: The may be submitted directly to Carrie Basic Science of Neural Prosthetics,” Wolinetz at [email protected]. the latest article in the Breakthroughs This new article explores the in Bioscience series. The Break- cutting-edge science of neural throughs in Bioscience series is a col- prosthetics, from cochlear implants lection of illustrated articles, published to artificial retinas to bionic arms, by FASEB, that explain recent develop- and describes the roots of these ments in basic biomedical research devices in centuries of fundamen- and how they are important to society. tal research. Today, millions of FASEB distributes this series, free of Americans use neural prostheses, charge, to members of Congress, whose origin can be traced back patient advocacy groups, educational to the 18th century physicist, Luigi organizations, members of the press, Galvani. Galvani’s discovery of and research advocacy partners. We highly encourage “animal electricity” in frogs was later identified as the members of the FASEB societies to use these materials electrical nerve impulse, which is the basic signaling in their own advocacy and education activities. The entire mechanism that nerves use to communicate with tis- series is available online at opa.faseb.org/pages/Publica- sues and organs. By the 19th century, research was tions/breakthroughs.htm or in hardcopy form by contact- being conducted on the cochlea as the main organ for ing the FASEB Office of Public Affairs at opa.faseb.org. sound, and following in Galvani’s footsteps, Princeton Recent titles in the series have included: psychologists E. Glen Wever and Charles Bray showed • Viruses, Cancer, Warts and All: The HPV that electrical impulses were involved in hearing speech Vaccine for Cervical Cancer from this organ. NIH-funded research in California • Breathtaking Discoveries: How Basic enabled scientists to discover exactly how the cochlea Research Led to Treatments for Asthma transmits speech sounds to the brain, and by the • Science, Serotonin, and Sadness: The 1970s, the first cochlear implant made its debut. Biology of Antidepressants The success of cochlear implants encouraged • Breast Cancer, Tamoxifen, and Beyond: researchers to study other neural processes, including Estrogen and Estrogen Receptors sight and the use of limbs. Many disciplines such as • Finding Chinks in the Viral Armor: Influenza, physics, physiology, ophthalmology, computer sci- AIDS, and Antiviral Therapies ences, mathematics, and engineering contributed to FASEB also welcomes suggestions for new topics further breakthroughs in neural prosthetics. Collectively, from member societies if scientists have ideas that meet these scientists fostered the development of bio- the objective of the series: basic research discoveries engineered devices that can close crucial gaps in nerve that have resulted in effective treatments or diagnos- signaling so that the deaf can hear, the blind can see, tics for medical conditions. The Breakthroughs series and amputees can have artificial limbs that feel and act is overseen by a subcommittee of the FASEB Science like their missing limbs. Policy Committee, chaired for the past decade by ASBMB and Peptide Society member Fred Naider, who Carrie D. Wolinetz is Director of Scientific Affairs and Public will be succeeded this winter by James Barrett. The Relations for the Office of Public Affairs at FASEB. She can be subcommittee is planning its next article, to be focused reached at [email protected].

6 ASBMB Today December 2008 news from the hill Obama Wins Presidency, Democrats Increase Majorities in the House and Senate BY PETER FARNHAM

s the polls closed in every state but Alaska, at 11:00 deficit spending and/or raising taxes. Thus, the chances of A pm Eastern time on Nov. 4, 2008, major news orga- large spending increases on biomedical and other scientific nizations around the country called the presidential race research in the near future, even with an otherwise sympa- for Senator Barack Obama. Senator John McCain made thetic administration and Congress, may be limited. it close (and interesting) in several key states, but for the Republican candidate, it did not matter in the end. Congressional Results As President, Obama is expected to be friendly toward Obama will be assisted by a more Democratic Congress. science. He recruited a very solid team of top scientists The Democrats entered Election Day with a slim 51-49 to advise him during the campaign, headed up by Nobel majority that included two Independents—former Demo- Laureate and ASBMB member Harold Varmus, President cratic Vice Presidential candidate Joe Lieberman and of Memorial Sloan-Kettering Cancer Center in New York. Socialist Bernie Sanders of Vermont. The results solidified He also described his views on science issues in detail Democratic control of the chamber, as they picked up at in his responses to a series of 14 questions sent to both least five seats; the new majority is 54 Senators (plus Lie- candidates earlier in the campaign by a group called berman and Sanders, who were not up for reelection this Scientists and Engineers for America. The October issue of cycle). As of this writing, three seats are still undecided, ASBMB Today also has information on Obama’s positions although the GOP leads in all three cases. However, the on certain key science issues. Democrats appear not to have reached the magic number Unfortunately, Obama will be limited in what he can of 60 seats; this is the number that would have allowed do early in his presidency. The nation faces massive fiscal them to invoke cloture and thereby cut off a filibuster. The problems: the wars in Iraq and Afghanistan, a $11 trillion ability to filibuster is the GOP’s sole remaining check on a national debt, annual budget deficits in the hundreds of greatly strengthened Democratic majority. billions, growing Social Security spending needs due to It is also enormously helpful to biomedical research that the aging “baby boomer” population, a new and expensive Sen. Tom Harkin (D-IA) won reelection easily; his seat was drug benefit under Medicare never in doubt, but, since he Part D, and the recent $700 is one of biomedical research’s billion bailout of the invest- two staunchest champions in ment banking and insurance the Senate, it was reassuring industries (which may rise to $1 to see that he prevailed. trillion or more before the res- It is not entirely clear what cue is finished). The continued the final count will be in the fiscal fallout of the subprime House, but Democrats are mortgage collapse will likely on track to pick up between exacerbate these problems. 20 and 25 seats. Albeit a Some of this involves manda- healthy gain, it does not rise tory spending required by law. to the levels predicted by This leaves very little money left some pundits in the days to pay for domestic discretion- leading up to the election. ary spending without resorting A democratic majority in the to some combination of unpal- range of 250-260 seats is atable alternatives: increased thus expected once the final

December 2008 ASBMB Today 7 news from the hill continued results are in, with the GOP relegated to approximately Speaker of the House Nancy Pelosi (D-CA) has issued 175 seats. yet another call for a lame duck session of Congress—a The day after the election, several leadership struggles final meeting of the 110th Congress, to occur prior to the had already begun to break out in the House. The most inauguration—to pass another economic stimulus package relevant to ASBMB’s interests is that Rep. Henry Waxman as quickly as possible. No details are available at this time, (D-CA) is expected to take on Rep. John Dingell (D-MI) for but ASBMB has joined the rest of the biomedical commu- the chairmanship of the powerful Energy & Commerce Com- nity to call for additional funding of scientific research in the mittee, which oversees NIH. prospective package. Finally, there were a variety of ballot initiatives around Other Developments the country, including Michigan’s Proposition Two, which As of this writing, Obama has offered the White House amends the state constitution to permit human embryonic chief of staff position to Rahm Emanuel, a Democrat who stem cell research with certain restrictions. According to the sits on the House Ways and Means Committee’s Health initiative, the embryos must have been created for fertility Subcommittee. During his three terms on the Hill, Emanuel treatment purposes; research may only be performed on has sponsored legislation on prescription drugs, public embryos that would have otherwise been discarded; and health campaigns for influenza vaccinations, and expan- the embryos may not be used more than 14 days after cell sion of a visa waiver program, suggesting that he may be division has begun. The initiative was approved by a margin familiar with some issues of interest to the ASBMB com- of 53, or 47 percent. munity. ASBMB, along with the coalitions it works with— While Democrats have many reasons to celebrate the which include FASEB, the Coalition for Life Sciences, and outcome of the 2008 election on purely partisan grounds, the Coalition for National Science Funding—will be push- biomedical researchers should also take heart in the knowl- ing the incoming administration to appoint knowledge- edge that, regardless of the amount of funding available able individuals to key staff positions and to give greater next year, science is likely to be given greater weight in the consideration to issues that affect biomedical research. next administration.

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Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4. Raetz, C.R.H. et al. (2006) J. of Lipid Res 47:1097-111. Phone 800-227-0651 (205-663-2494 International) or Email [email protected] for details of Avanti’s selection of lipids of unparalleled purity visit www.avantilipids.com FROM RESEARCH TO CGMP PRODUCTION - AVANTI’S HERE FOR YOU news from the hill continued Paul Rogers, “Mr. Health,” Passes Away at 87 BY PETER FARNHAM

aul Rogers, known as “Mr. Health” for his 24 years’ over his long career. People around the world can be Pwork as a Florida congressman, died unexpectedly in thankful for all that he did on behalf of public health.” mid-October. Hundreds of friends and colleagues turned The former chairman of ASBMB’s Public Affairs out on Oct. 20 to mourn him at a memorial service at Advisory Committee, Bill Brinkley, was attending a recent Washington National Cathedral, a fittingly grand setting Institute of Medicine meeting when word of Rogers’ for a man who will be sorely missed by biomedical advo- death was announced. As Brinkley told ASBMB Today, cates everywhere. “During the campaign to double NIH funding, Paul would Rogers entered Congress in 1954 and served in 11 take me by the arm and usher me into the congressional consecutive Congresses, until Jan. 3, 1979. He chose offices of both friends and staunch opponents with his not to run for reelection to the 96th Congress, even big smile and say, ‘This is Dr. Bill Brinkley, a scientist from though he had won his previous election with 91 percent the great Texas Medical Center down in Houston, and of the vote. he wants to tell you why we need to double the budget Rogers served as chair of the Subcommittee on for health research at NIH!’” After one such meeting with Health and the Environment from 1971 to 1979. He was a staunchly conservative senator initially opposed to a key architect of the adoption of the National Cancer the doubling, Rogers told Brinkley that the meeting was Act of 1971, the Medical Device Amendments Act of so successful that even this senator “has come over to 1976, The Health Maintenance Organization Act, the our side—now that is something; we are really making Emergency Medical Service Act, the Medicare-Medicaid progress!” Anti-Fraud and Abuse Amendments of 1977, the Clean Kevin Mathis, a lobbyist who worked with Rogers on Air Act of 1970, and the Safe Drinking Water Act. the campaign to double NIH’s funds, gave a glimpse of After leaving Congress, Rogers joined the Washington Rogers’ puckish sense of humor. After a meeting with D.C. law firm of Hogan & Hartson, and in addition to his Rep. John Spratt (R-SC), Rogers noted, “That was Jack law practice, was very generous with his time, participat- Spratt.” After a perfectly timed pause, he added, “He can ing in many charitable causes that advanced his passions eat no fat!” for health and quality of life. This passion led him to work Research!America President Mary Woolley spoke very hard with the Campaign for Medical Research, of eloquently of Mr. Roger’s legacy at his memorial service. which ASBMB was a part, in the late 1990s to double the “Please join me in taking a deep breath. And join me in NIH’s budget, conducting hundreds of meetings between savoring that breath. We can savor a deep breath of air scientists and members of Congress to advocate for the this morning because the air we’re breathing is clean. doubling plan. In recognition of his contributions to the “And we can savor the water we drink; we can revel in nation’s health, the main plaza at NIH was named in his our nation’s priceless lakes and rivers, because our water honor in 2001. is clean. Rogers was eulogized at his memorial service by sev- “We can rejoice in the lives of children who have over- eral people who knew him well, including his friend and come diagnoses of cancer. former law partner, Chief Justice of the Supreme Court “We can celebrate octogenarians who flourish in ways John G. Roberts Jr., who lauded him as an extraordi- unthinkable only a few decades ago. narily gracious man. As Justice Roberts said, “No one “For all these blessings, and for many more, we have would exit an elevator after him or go through a doorway Paul Grant Rogers to thank.” behind him.” Rogers’ attitude toward basic biomedical research In a statement released upon news of Rogers’ death, can be summed up best by one of his favorite remarks: NIH Director Elias Zerhouni noted that “All of us at NIH “Without research, there is no hope.” are deeply saddened...We have lost one of our true champions for biomedical research. His dedication, intel- Peter Farnham is public affairs officer of the Society. He can be lect, and disarmingly warm style reaped many successes reached at [email protected].

December 2008 ASBMB Today 9 asbmb member spotlight Brady Honored with National Costello Named HUPO Medal of Technology and Discovery Award Winner Innovation Catherine E. Costello, Director of the Roscoe O. Brady, Scientist Emeritus at the University School of Medicine Mass National Institute of Neurological Disorders Spectrometry Resource, was awarded the and Stroke at NIH, was honored with a Human Proteome Organization’s Discovery 2007 National Medal of Technology and Award in Proteomics Sciences. She Innovation. received the award for her contributions “to President Bush presented Brady, five the structural elucidation of glycolipids and other individuals, and two corporations, lipids and of post-translational modifications with his medal at a White House ceremony that are involved in the onset and progress in September. The medal is the highest of infectious and parasitic diseases, misfolding, disorders, honor for outstanding contributions to the nation’s economic, and cardiovascular disease.” environmental, and social well-being through the development and Costello is an internationally known leader in glycomics and gly- commercialization of technology products. The medal was created coconjugate analysis. Her research focuses on developing the ini- by Congress in 1980 and has been presented by the President of tial techniques and applications of high performance tandem mass the United States since 1985. spectrometry for glycan and glycolipid analysis. She was the first Brady was honored for his discovery of the enzymatic defects to apply matrix-assisted laser desorption ionization time-of-flight in hereditary metabolic disorders such as Gaucher disease, (MALDI-TOF) mass spectrometry for site-specific profiling of glyco- Niemann-Pick disease, Fabry disease, and Tay-Sachs disease. protein glycans and for the direct analysis of glycolipids from thin- These studies led to Brady’s development of diagnostic, carrier layer chromatographic plates. To address the problems caused by detection, and prenatal tests for several of these disorders. He and metastable decomposition of MALDI-generated ions, she and her his co-workers also developed effective enzyme replacement ther- colleagues developed the high-pressure MALDI source for fourier apy for patients with Gaucher disease and Fabry disease. Brady is transform ion cyclotron resonance mass spectrometry (FTMS) and currently investigating substrate depletion and molecular chaper- applied it to the analysis of thin-layer chromatography-separated one therapy for patients with metabolic storage disorders. glycolipids and protein digests. She has also made contributions to the structural elucidation of glycolipids and lipids, and of protein post-translational modifications that are involved in the onset and Bruice Honored with progress of infectious and parasitic diseases, protein-misfolding Linus Pauling Medal disorders, and cardiovascular disease. Thomas C. Bruice, Professor of Chemistry and Biochemistry at the University of Stroud to Receive Anatrace California, Santa Barbara, has been awarded the 2008 Linus Pauling Medal. Membrane Protein Award The medal is given annually by the Oregon, Robert Stroud, Professor of Biochemistry & Portland, and Puget Sound Sections of the Biophysics and Professor of Pharmaceutical American Chemical Society; it recognizes Chemistry at the University of California, outstanding accomplishments in chemistry San Francisco, has been selected to in the spirit of and in honor of Linus receive the Biophysical Society’s 2009 Pauling, a native of the Pacific Northwest. Anatrace Membrane Protein Award. Bruice has published over 530 research papers in 32 discern- The Anatrace Membrane Protein Award able areas related to biochemical problems. He was involved in was established to recognize an outstand- inventing the term “bioorganic chemistry” and helped to define ing investigator who has made a significant the field. Significant advances have been made in his laboratory contribution to the field of membrane protein research. Stroud was in the elucidation of the catalytic processes in acyl and phos- selected to receive the award for his contributions to transmem- phate transfer reactions, the mechanisms of cofactor reactions brane biology and for pioneering new methods that allow mem- (pyridoxal, flavins, lipoic acid, and dihydronicotinimides), and brane to become tractable. He will receive the award at metalloporphyrin chemistry. More recent areas of investigation the annual Biophysical Society meeting in Boston this spring. include the design, synthesis, and study of putative anti-sense Stroud’s research has focused on elucidating the molecular and anti-gene agents as well as the use of computational mechanisms of biological processes at the protein level. His lab methods in the study of reaction mechanisms and in particular studies several integral membrane proteins including aquaporins, enzyme catalysis and drug design. the ammonia channel, and glycerol channels. Stroud is also the Bruice is a member of the National Academy of Sciences, the Director of the Membrane Protein Expression Center (MPEC) and American Academy of Arts and Sciences, a Guggenheim Fellow, the Center for Structures of Membrane Proteins, both at UCSF. and a fellow of the Royal Society of Chemistry.

10 ASBMB Today December 2008 asbmb member spotlight Please submit member-related news to [email protected] Karger Awarded Torbern Prestwich Wins Volwiler Bergman Medal Research Achievement Award Barry L. Karger, Founder of the Barnett Glenn D. Prestwich, Presidential Professor Institute of Chemical and Biological Analysis of Medicinal Chemistry and Special at Northeastern University, was recently Presidential Assistant for Faculty awarded the Torbern Bergman Medal by Entrepreneurism at the University of Utah the Analytical Division of the Swedish College of Pharmacy, received the Volwiler Chemical Society. Karger, who is also the Research Achievement Award from the James L. Waters Chair in Analytical American Association of Colleges of Chemistry at the Barnett Institute, received Pharmacy. Prestwich was honored for his the medal in recognition of his work in outstanding research and contributions to aiding the development of separation science as a tool for the the field of pharmaceutical sciences. analysis of biological molecules. Prestwich’s research focuses on new reagents for lipid signal- The Bergman Medal, which is presented every other year to a ing in cell biology and cancer treatment, and biomaterials for single recipient, is among the most prestigious analytical chemistry wound repair, cartilage repair, stem cell culture, tissue engineering, awards. It is given to those working to make a “paradigm shift in scar-free healing, and toxicology and xenograft models. life science” through mass spectrometry. “Glenn is an exceptional leader and teacher. He is not only Among his career-defining accomplishments, Karger helped known for his incredible contributions to pharmaceutical educa- develop polymer matrices used in the Human Genome Project. tion, but for a commitment to research that is vital to the academic His current research focuses on the integration of modern community,” explained Lucinda L. Maine, AACP executive vice separation systems with mass spectrometry for proteome and president and CEO. “It is an honor to present him with this presti- biomarker analysis. gious award.” Karger was also recently elected as an honorary member of Prestwich also holds adjunct appointments in the Departments the Hungarian Academy of Sciences, an honor rarely extended to of Chemistry, Biochemistry, and Bioengineering at the University of non-Hungarian citizens and named recipient of this year’s Csaba Utah. During his 32 years as a faculty member, he has published Horvath Medal. more than 600 technical papers, patents, and book chapters, including popular articles in National Geographic and Scientific Stubbe Presented American. with Kirkwood Medal JoAnne Stubbe, Professor of White Recipient of Avanti Award Chemistry and Professor of Biology at Stephen H. White, a Professor at the Massachusetts Institute of Technology, was University of California, Irvine, will receive presented with the 2008 Kirkwood Medal the Biophysical Society’s 2009 Avanti this past spring. Stubbe received the award Award in Lipids at the Society’s annual for her work in mechanisms of enzymatic meeting in Boston this spring. White was reactions and biosynthetic pathways. The selected to receive the award for his novel award, which is presented biennially by Yale findings in the areas of membrane structure University and the American Chemical and protein insertion into membranes. Society New Haven Section, honors the late John G. Kirkwood, White’s laboratory focuses on biophysi- former Sterling Professor of Chemistry and Chairman of the cal problems related to the folding and stability of membrane Department at Yale. proteins and is part of the UCI Structural Biology and Molecular Stubbe’s major research efforts have focused on the mecha- Biophysics graduate program. Specifically, he looks at the follow- nism of nucleotide reductases. Her work has led to the design and ing areas: membrane and stability, energetics of synthesis of several nucleotide analogs that have potential anti- protein-bilayer interactions, experimentally determined hydropho- tumor, anti-virus, and anti-parasite activity. Currently, Stubbe has bicity scales, translocon-assisted folding of membrane proteins, four main research interests: 1) the mechanism of natural product structure of fluid lipid bilayers, molecular dynamics simulations of DNA cleavers; 2) the mechanism and regulation of ribonucleotide membranes and proteins, and antimicrobial peptides. reductases; 3) polyester biosynthesis; and 4) the mechanism, White, who served as the President of the Biophysical Society structure, and regulation of the purine biosynthetic pathway. She from 1996 to 1997, has received many other honors and awards has a long list of awards and honors, including election to the in the past, including the Kaiser-Permanente Award for Excellence National Academy of Sciences. in Teaching (1975 and 1992) and the Biophysical Society Distinguished Service Award (1999).

December 2008 ASBMB Today 11 asbmb news Retrospective: Anthony G. San Pietro

nthony G. San Pietro, professor emeritus nase, then reduces NAD using reduced NADP. Aat Indiana University, passed away on In 1962, San Pietro joined the Charles F. Sept. 13, 2008, at the age of 86. Kettering Research Laboratory in Yellow Born on Apr. 22, 1922 in Brooklyn, Springs, OH, where he was involved in NY, San Pietro originally aspired to the creation of a first-rate laboratory in become a singer. When he was in Photosynthesis and Nitrogen Fixation high school, he purchased booklets Research. While at the Kettering lab, of song lyrics from street vendors he extended his research to include and emulated the popular sing- chromatophores of photosynthetic ers of the time. Despite his obvious bacteria and also made time to teach talent, however, he instead chose a a biochemistry course at Antioch career path in scientific research and College. education. He graduated from New San Pietro moved to Indiana Uni- York University in 1942, after which he versity, Bloomington in 1968 to chair entered the Army Specialized Training the Department of Plant Sciences, a Program where he studied electrical engi- position he held until 1977. While serving neering. Upon completing the program, he as chairman, he maintained an active labo- joined the Manhattan Project in Los Alamos, NM, ratory for investigating the mechanisms of the as a member of its Biochemistry Group. light-dependent reactions of photosynthesis and pub- After finishing his military service, San Pietro enrolled lished over 160 papers. In 1975, San Pietro was given in graduate school at Columbia University and received the title of distinguished professor of Plant Biochemistry, his Ph.D. in Biochemistry in 1951. He then did a two-year and in 1980, he was appointed science adviser to the postdoctoral fellowship at Johns Hopkins University, after Office of the President of Indiana University. In 1983, he which he became an assistant professor in Biology at the was honored by election to the National Academy of Sci- McCollum-Pratt Institute. He was promoted to associate ences. San Pietro was also awarded an honorary doctor professor in 1959. of science degree by Purdue University in 1992, the same During his time at Johns Hopkins University, San year he retired from the Indiana University faculty. Pietro isolated an enzyme from chloroplast extracts that During his 50 years in science, San Pietro traveled was needed for the photochemical reduction of NADP extensively and collaborated with scientists from Japan, and suggested it be named “photosynthetic pyridine Europe, England, and Israel. He also edited several of the nucleotide reductase” (PPNR). Several years later, it photosynthetic volumes of Methods in Enzymology and was shown that PPNR and a new electron carrier called served on the Editorial Board of the JBC. “ferredoxin,” discovered in the hydrogenase system of After his retirement, San Pietro continued to make Clostridium pasteurianum, were functionally similar. Thus, contributions to the educational and scientific communi- PPNR became known as ferredoxin. ties, participating in Indiana University’s Faculty and Staff San Pietro continued his work on photosynthesis and for Student Excellence (FASE) mentoring program until later isolated transhydrogenase, the enzyme that trans- 2003. As a consultant to the Vice-Chancellor for Under- fers hydrogen from NADPH, formed by photosynthetic graduate Education at Indiana University-Purdue Univer- pyridine nucleotide reductase, to NAD. This was the basis sity Indianapolis, he helped guide the University’s efforts of his Transhydrogenase Theory, which states that illumi- to develop a community, state, and national alliance for nated grana reduce NADP in the presence of photosyn- enhanced minority enrollment in science and engineering thetic pyridine nucleotide reductase and transhydroge- education.

12 ASBMB Today December 2008 special interest Science’s Role in Foreign Policy BY ALLEN DODSON

he world of foreign policy has seen “shuttle diplo- many scientists view security regulations with a lack of Tmacy” and “ping pong diplomacy,” but is it ready confidence and distrust. Keynote speaker John Hamre, a for biochemical diplomacy? The new Center for Science former Deputy Secretary of Defense, argued that increased Diplomacy at the American Association for the Advance- cooperation could help eliminate ineffectual regulations, ment of Science (AAAS) held a conference in Washington noting that the intelligence community often doesn’t know titled, “Science, Diplomacy, and International Coopera- what questions to ask and that scientists are, in some tion” to address this question. The event focused primarily cases, taking the necessary security precautions on their on how collaboration between scientists can help broaden own. Hamre suggested that scientists have a role to play as foreign policy goals, and called for increased cooperation sentinels over dual use technologies, which have legitimate between scientists and policymakers. Speakers agreed research applications but could also be exploited by ter- that, regardless of popular opinion of American policy rorists. Vaughan Turekian, Chief International Officer of in general, the world continues to hold our science and AAAS, agreed that scientists should be involved in drafting technology advances in high esteem and wants to establish protections against this “dark side” of biomedical research collaborations with our scientists and institutions. to produce regulations that are both manageable and effec- tive. As Hamre put it, the goal should not be loosening Improving Relations through Research rules but rather re-writing them to ensure that the rules Rep. Brian Baird (D-WA), chair of the Research and that remain on the books are there because of their impor- Science Education subcommittee of the House Science tance to U.S. security. Committee, gave opening remarks. He emphasized that the personal and professional relationships formed Regulations and International Collaboration between scientists can span borders and help deal with Issues related to visas were mentioned repeatedly during global issues like climate change, food supplies, and drug- the conference. Numerous panelists noted that foreign resistant infectious diseases. However, he also warned nationals face hurdles applying for visas, work permits, that these goals may need to be accomplished with little or even visits to the United States. Hamre observed that or no additional funding, because of the ongoing financial we have closed our doors just as other nations are invest- crisis and the other long-term financial commitments on ing more in order to build local capacity and attract their the nation’s books. expatriate scientists home. Funding was also discussed; The conference featured several testimonials about currently many funding agencies do not fund overseas col- cases in which collaborations started by scientists to laborators, even when the amounts of money in question pursue research have the potential to improve foreign are small and would further the work of funded American relations. For example, Stuart Thorson from Syracuse researchers. It was also noted that international policies can University summarized ongoing collaborations between impact universities in major ways. his institution and a North Korean university, and the New America Foundation’s Patrick Doherty described The New Administration a delegation of U.S. scientists seeking approval from the The next few months present an opportunity to re-evaluate United States to travel to Cuba. policy roles at the start of a new administration. Although we hope for improvements in the state of research and Science and Biosecurity Regulations education, perhaps it is also time to anticipate a new role as In discussions on biosecurity, participants agreed that there ambassadors—official or informal—in a scientific enter- needs to be better communication and understanding prise that transcends borders. between the intelligence and scientific communities. Cur- rently, many security experts are concerned that scientists Allen Dodson is an ASBMB Science Policy Fellow. He can be fail to do enough to safeguard sensitive information, and reached at [email protected].

December 2008 ASBMB Today 13 special interest ASBMB Round Table: Jim Wells and Mary Woolley BY NICK ZAGORSKI

im Wells, University of Cali- Wells: Another way to look fornia, San Francisco chair at it is that our health situa- and professor of Pharmaceu- tion is not necessarily better, only some of the diseases ticalJ Chemistry and professor of have changed. One hundred Cellular and Molecular Phar- years ago, if an individual got macology, and Mary Woolley, infected with polio, his family president of Research!America, would just accept it as a mat- have both been long-time advo- ter of course—it was God’s cates of improving the global will or something. Today, we health system. This past summer, certainly wouldn’t accept an they each caught the attention explanation like that. But, of Science Editor-in-Chief Bruce say your father gets diagnosed Alberts, who suggested they join their unique perspectives— with congestive heart failure, the cardiologist might tell Wells’ firsthand knowledge of drug research and development you, “Well, I guess his heart is just wearing out.” And 50 and Woolley’s 25 years of editorial, publication, and outreach years from now, someone will look back and say, “I can’t believe they used to give such crazy explanations.” efforts—for an editorial in the journal. Together, they laid out some of the problems in the worldwide health arena and sug- gested that a populist movement, à la Al Gore’s environmen- ASBMB: For those people already cognizant of the looming tal crusade, might be needed for public health as well1. The problem, one of their biggest worries may be the threat of a two recently sat down at the ASBMB round table and gave new pandemic rivaling the Spanish Flu of 1919. But do you some more insight into their populist proposal. both believe that another potentially serious crisis could arise as well? Wells: Definitely. As our population ages, we’re going to ASBMB: One of the ways that the climate change movement wind up with many more people with diabetes, Alzheim- got momentum was through the vivid images of shrinking er’s, cancer—all diseases that, under our current model, glaciers highlighting the downward trend of our environ- will require long periods of care and treatment, and thus ment over the past 50 years. However, in regards to public will be a huge financial burden. health, most people probably think we are better off than we were 50 years ago (longer lifespans, better vaccines, etc.). Woolley: I agree. In addition, one important looming Will that make it more difficult to convince them that we problem that we did not have a chance to expand on in the are, in fact, on the precipice of a crisis? editorial is the economic cost of a deteriorating health sys- tem, and it’s big. And tough economic times are inherently Woolley: Well, I think the “it’s not so bad attitude” may linked with healthcare costs, which we can see now. People be exactly the way most people felt about climate change are avoiding refilling their drug prescriptions or not visiting when the scientific experts first brought it up—well before referring physicians because they’re worried about the cost. Al Gore brought it to the masses—because for both global warming and global health, the majority of the problems initially lay below the surface like an iceberg. So, things ASBMB: Despite the many effects (and victims) of climate appear all right, but you can see many disturbing signs change, polar bears have become one of the more popular about our health if you know where to look: the rising obe- symbols of the crisis; do you see some particular disease sity epidemic, the emergence of SARS and other diseases, that might strike a similar chord to captivate the public? Or and even scientific reports that suggest average lifespan do you think focusing too narrowly might be detrimental to might be plateauing out. advocating for global health as a whole?

14 ASBMB Today December 2008 special interest

Wells: I think it’s great that some people or places bring had to convince Congress to pass a law mandating seat attention to specific diseases, for example, St. Jude’s belts in all cars, then we still had to convince motorists Children’s Hospital and all the great work they’ve done for to wear them as an act of habit. There have been simi- childhood cancers. But, it’s vital that these individual lob- lar initiatives in health education, like having fast food byists make sure to highlight that the underpinnings of all restaurants display their nutritional information, but we these diseases are interconnected, like the links between really haven’t even begun to scratch the surface of things obesity and diabetes or cancer and inflammation. we can do. Woolley: I agree with Jim; using examples can certainly Wells: I think that also brings up an important point; help illustrate the problem, but we don’t want to over- one of the amazing things about the environmental shadow the big threat to our well-being, which is that movement is that Al Gore said that it may take a century health for everybody is not where we need to be. of work to halt the global warming crisis, but that didn’t deter any enthusiasm. So we need to stress, to the pub- ASBMB: In looking for the Al Gores of public health, what lic and policymakers, the similar need for time to bring kind of individual would you envision as ideal? What traits about changes in health. Unfortunately, both research should he or she have for the best chance of success? And scientists and pharmaceutical companies have been doing perhaps most importantly, should the spokesperson be a a lousy job relaying their expectations, often setting scientist or not? unreasonable goals, and that can sour the public when Wells: I’ve discussed this at many meetings, and I you don’t meet them. believe that we definitely should not have a scientist as the key champion. The reason is that we’re not looking for ASBMB: Speaking of pharmaceutical companies, do you a Carl Sagan-type of figure, someone to inspire and fasci- think these industries could be an obstacle in a global health nate us about science. We need someone who understands movement? Or, is it important to have Pharma on hand as science but has to come in and communicate the vulner- an ally in this endeavor to go from ‘crisis management’ to ability of the global health situation, point out the medi- ‘cure’? cal, economic, and global security risks, and call people out to action. In that regard, a pure scientist-spokesperson Woolley: I think Pharma is an ally. We will always need may lead to a perception that he or she has an underlying treatment advances before we get to cures, themselves self-interest for funding. often Pharma-based, as are preventions such as vaccines. However, the Pharma pipeline is in trouble right now, and Woolley: Yes, the face of our effort has to convey both there are also regulatory and litigation challenges hinder- integrity and plausibility. In looking at possibilities, what ing progress. We need a combination of innovation and Al Gore brought to the table was political savvy as well as a long-standing history of effort in the climate arena, plat- business savvy, smarter public policy, and advocacy by forms that should not be overlooked. The kind of people patient groups and others to bring the promise of research that have been equally as stunning in the health area for global health to fruition. already include Bill Gates, Mike Bloomberg, and Hillary Wells: I know pharmaceutical companies frequently Clinton. Bono provides another good example; while his get maligned and vilified and sometimes for good rea- efforts are more specific to global poverty, he does exem- sons. But I’ve been in the pharmaceutical business, so I plify someone dedicating his life’s work to a cause. know that the rank and file researchers, their hearts are in the right place, trying to develop better drugs to help people. And we’re definitely going to need them, because ASBMB: Besides increased funding for research, a big aspect of a populist endeavor is education and service; i.e. what these still are the people that have the knowledge and can you do to help? Do you have any thoughts on getting a resources to develop drugs, although it’s encouraging to good education message across, especially considering many see academia beginning to work more with this area. current efforts at health education (healthy diet, regular screenings, etc.) seem to have limited effect? Nick Zagorski is a science writer for ASBMB. He can be Woolley: I do believe health messages have been having reached at [email protected]. positive effects; it’s just been at a slow pace. It’s important to understand that real behavioral change takes time and REFERENCE a combination of efforts. Take seat belts, for example; first, 1. Wells, J., and Woolley, M. (2008) A Populist Movement for Health? we had to prove conclusively that they save lives, then we Science 322, 15.

December 2008 ASBMB Today 15 special interest Keeping Women in Science BY NICOLE KRESGE

ecent data has shown that while equal numbers of and physics. One survey collected information on depart- Rwomen and men enroll in graduate school and earn mental policies, recent tenure and promotion cases, and doctoral degrees in the biomedical sciences, women only recent hires in almost 500 departments. The other survey comprise about 25 percent of tenured faculty. The cause of gathered information from a stratified, random sample of this phenomenon, often referred to as “the leaky pipeline,” about 1,800 faculty members on demographic character- has garnered much investigation over the past several years, istics, employment experiences, the allocation of insti- including the National Academy of Sciences’ Beyond Bias tutional resources such as laboratory space, professional and Barriers report. Proposed explanations for this trend activities, and scholarly productivity. include reasons such as: women leave the workforce to act Canizares closed by saying that he believes that one of as caregivers and raise families; women are less competitive the reasons women are leaving science is the prolonged than men; women devote more time to teaching and men- amount of time it takes to obtain a faculty position, due to toring than men; and lastly, that women don’t have many the increasing length of postdoctoral fellowships and the female role models in science. time to tenure. The system is problematic, he believes, and One of the latest attempts to fix the leaks in the pipeline we need to examine the underlying structure of the profes- came in the form of a workshop this past September called, sion to see if we can adjust it. One way to do this, Canizares “From Doctorate to Dean or Director: Sustaining Women suggested, is to involve professional societies in the discus- through Critical Transition Points in Science, Engineer- sion and encourage them to implement change. ing, and Medicine.” The workshop was organized by the Joan Girgus, professor of psychology and special National Academies of Sciences’ Committee on Women assistant to the dean of the faculty for issues concern- in Science, Engineering, and Medicine (CWSEM) and was ing faculty diversity at Princeton University, followed sponsored by the National Institutes of Health’s Office of Canizares’ presentation by turning the focus to a meet- Research on Women’s Health and the Kauffman Founda- ing that occurred at MIT in 2001, between the leaders of tion. The premise of the workshop was that women were nine research universities. This meeting focused on how leaving the sciences at key transition points in their careers, universities dealt with the professional lives of women, such as the step from postdoctoral fellow to assistant profes- and the meeting attendees agreed to analyze the salaries sor, and if these “leaks” were fixed, more women might be and university resources provided to women faculty, work retained in higher level positions in the sciences. toward a faculty that reflects the diversity of the student body, and to reconvene in one year. Assessing Gender Differences The MIT nine universities have been meeting every year and Providing Support since then, but more recently, their focus has turned from The workshop started with a presentation by Claude the professional lives of faculty to how faculty members, Canizares, vice president for research and associate postdoctoral fellows, and graduate students can juggle work provost at Massachusetts Institute of Technology and and family. She argued that all three groups need additional the Bruno Rossi professor of Physics. Canizares spoke support and suggested we provide a variety of resources to about an upcoming report on a study by the National choose from, such as maternity leave, tenure clock exten- Research Council titled, “Assessing Gender Differences sion, workload relief, dependent care travel funds, and in the Careers of Science, Engineering, and Mathematics on-campus child care. By implementing these programs, Faculty.” Due to NRC rules, Canizares couldn’t divulge institutions are making it clear that it’s okay to want both the results of the study until it was published, but he a thriving career and a family. Girgus concluded by stating did explain that the congressionally mandated report that universities must think of these supports as essential was based on two surveys of faculty and departments at for a stimulating work environment and find the funds to research I universities in the fields of biology, chemistry, provide them, or we may end up losing our best and bright- civil engineering, electrical engineering, mathematics, est women and men.

16 ASBMB Today December 2008 special interest

Women and Medicine June Osborn, president emerita of the Josiah Macy, Jr. Foundation, then gave a presentation on the 2007 Macy Foundation’s Report on Women and Medicine. She explained that although the state of women partici- pating in medicine is better than that of women partici- pating in research science, the number of women faculty members participat- ing in academic medicine is still low. She believes that a lack of visible female lead- ership has caused a runoff of women. The president of the Association for Women in Science (AWIS), Phoebe Leboy, followed Osborn’s Figure 1 presentation with a discus- sion on the decline in women involved in basic science in of time what you want and negotiate for it, don’t be passive academic medicine. She presented statistics which revealed aggressive, and finally, find out what is expected of you in that there is a 50 percent decrease in the number of women your new position. during the transition from postdoc to assistant professor. Susan Wessler, a professor at the University of Georgia, This decline is occurring because women are not applying spoke next about making the transition from assistant pro- for assistant professor positions, Leboy explained; instead, fessor, to associate professor, to professor. She asserted that women are leaving the academic workforce for more the negative perception that it is difficult to have a family women-friendly professions, such as science writing and and a career at the same time leads to a leaky pipeline. Her consulting. Leboy believes that women are encountering solution was to promote the idea of academic research as a obstacles in the pipeline, including family issues; a chilly, family-friendly job that allows flexibility. isolating climate for women; and a culture designed for, A second panel addressed careers in industry. Elizabeth and by men. In order to alleviate this problem, she recom- Donley, chief executive officer at Stemina Biomarker Dis- mended that institutions implement mentoring and net- covery, Inc., Andrea Vergara-Silva, senior scientific liaison working programs, develop more family-friendly policies, at Astellas Pharma U.S., Inc., and Lydia Villa-Komoraff, decrease sexist behavior, and provide a more welcoming chief executive officer at Cytonome, Inc. spoke of their workplace culture for women. career paths and the compromises they made to raise their families. Despite the fact that industry is by far more family- Some Personal Stories friendly than academia, all three women revealed that they The next part of the workshop featured a panel of women encountered glass ceilings and were discriminated against at who spoke about the transition points in an academic certain points in each of their careers. career. Pardis Sabeti, a new faculty member at Harvard Uni- versity and the “proud mother of a new lab” talked about Interdisciplinary Science transitioning from postdoc to assistant professor. She had a The final workshop panel looked at the rise of interdisci- lot of advice for young scientists including: figure out ahead plinary science and how it affects women and their careers.

December 2008 ASBMB Today 17 special interest continued Alice Agogino, the Roscoe and Elizabeth Hughes profes- male. The current UNC-Chapel Hill BIRCWH program sor of Mechanical Engineering at the University of Cali- contains 22 women and two men from a diverse array of fornia, Berkeley, began by remarking that many fields fields including pathology, psychology, health education, have “entrenched” the status quo by making it difficult and oncology. for women to succeed. Fortunately, over the past several years, new interdisciplinary areas such as bioengineer- Having a Career and a Family ing and environmental engineering have emerged, and A final presentation by Kathleen Christensen of the women have ventured into these new fields of science Alfred P. Sloan Foundation addressed the fit between that have little or no entrenched gender bias. family and career. Christensen used some statistics from The next panelist was Stacey Gabriel, director of the a University of California, Berkeley survey to point Genetic Analysis platform and the National Center for out that although 40 percent of assistant professors at Genotyping and Analysis at the . She the University are women, this number falls sharply to talked about the Broad Institute as a new model of col- 18 percent when looking at the number of full female laborative science that brings together scientists from professors. She claims that having a family affects career MIT, Harvard, and other institutions to work on prob- formation and pointed out that women with babies are lems in genomic medicine. Although there are more 28 percent less likely than women without babies to male research faculty members than female members at enter a tenure-track position (Figure 1), and that while the institute, Gabriel pointed out that equal numbers of 70 percent of male tenured faculty are married with men and women hold the role of director. children, only 44 percent of female tenured faculty are The final panelist of the workshop was Eugene Orrin- married with children. ger, a professor of Medicine at the University of North Christensen feels part of the problem is that aca- Carolina-Chapel Hill. He talked about the Building demic careers are thought of as straight-line trajecto- Interdisciplinary Research Careers in Women’s Health ries when in reality, they are more jagged paths with (BIRCWH) Program, which was created by the Office of plateaus, accelerations, and decelerations. As a solution, Research on Women’s Health at NIH. BIRCWH awards she suggests we make careers more flexible and realign are given to individual institutions and are designed to the academic career path to fit the needs of an increas- identify junior faculty scholars whose primary focus ingly diverse workforce. Her suggested career flexibility was women’s health research and then train them in an policies include extending the time to tenure, adding on interdisciplinary manner. Of the BIRCWH program and off ramps through leave policies, including slow- scholars, 79 percent are female and 21 percent are down periods with reduced appointments, allowing delayed entry to foster later-than-usual career starts, and implementing phased retirement.

Resources The Future • The workshop program and findings, as well as The workshop concluded with a summary of findings, the individual presentations, can be found at: themes, and next steps. Workshop attendees agreed www7.nationalacademies.org/cwsem/ that most of the issues discussed impact both men and • The text of Beyond Bias and Barriers: Fulfilling the women, just not at the same level or in the same man- Potential of Women in Academic Science and Engineering ner. It was suggested we look at what we can apply from can be read online at books.nap.edu/catalog.php?record_ successful fields and institutions and involve both men id=11741 and women in future discussions. Some of the next steps • The National Research Council Report, “Assessing identified by workshop coordinators included strength- Gender Differences in the Careers of Science, ening the mechanisms of information dissemination, Engineering, and Mathematics Faculty” will be regularly engaging representatives from professional published by the end of the year and can be ordered societies, and addressing basic issues impacting career at books.nap.edu/catalog.php?record_id=12062 transitions overall, such as the time it takes to earn a degree, and then focusing on issues impacting women • The Macy Foundation Report on Women and Medicine in particular. can be found at: www.josiahmacyfoundation.org/index. php?section=publications Nicole Kresge is the editor of ASBMB Today. She can be reached at [email protected].

18 ASBMB Today December 2008 publishing series Grammar and Writing Tips

ave you ever wondered why an accepted manuscript Tip 3: Compound Sentences Hsubmitted to the JBC doesn’t necessarily read quite “These particles do not bind nucleic acid and plasmid the same when returned in proof form for your review? DNA remains in the supernatant.” Scientific research demands accuracy; thus, scientific The above sentence is missing something. Cadmus writing itself should reflect this with razor-sharp preci- copyeditors would change this to be grammatically sion and clarity. Cadmus Communications works to correct. This compound sentence needs a comma clarify manuscripts for the reader by reviewing and, if before “and.” Otherwise, readers may “stumble” at first necessary, correcting grammar, spelling, and punctuation. glance, mistakenly believing that the particles do not We try to enforce consistency throughout an article so as bind nucleic acid and plasmid DNA. But wait—isn’t not to “jar” the flow of the article. Below are four topics plasmid DNA a nucleic acid? Instead of accidentally that Cadmus editors would like to share with ASBMB forcing your audience to reread a sentence containing Today readers—in essence, a few reasons why we do what two independent thoughts, a comma should be placed we do! These editorial “tidbits” may provide authors with before the “and” in all compound sentences, leaving some explanations why certain editorial revisions have the reader free to enjoy the rest of your article. been made to their articles. Tip 4: Subject/Verb Agreement Tip 1: Verb Tense “Furthermore, the relative expression and the spec- JBC authors may have encountered an author query simi- trum of growth factors present in the individual lar to the following: “?/Author: Verb tense: The past tense microenvironment is not defined…” is used for what was done and observed in your experi- The subject and verb should always agree with each ments; the present tense is used for established facts other, not with a word that comes in between them. The (already published work) or general truths. Therefore, correct sentence follows: “Furthermore, the relative XXX has been changed to ZZZ.” expression and the spectrum of growth factors present As they do when they are speaking, journal authors in the individual microenvironment are not defined...” frequently alternate between the past and present tenses Both the relative expression and the spectrum are not when writing an article. Here is a good tip for authors defined; therefore, the plural form is correct. Watch- to follow: when quoting or discussing previously pub- ing out for when to use a singular verb (“is,” “either,” lished work, an author should use the present tense in the or “was”) versus a plural verb (“are,” “both,” and “Introduction” and “Discussion” sections. When refer- ring to your own work, however, which has not yet been “were”) is easier than you may have thought! published, results should be discussed in the past tense, i.e. in the “Introduction,” “Materials and Methods,” and So, the next time you submit an article to the JBC “Results” sections. Another useful rule of thumb: “previ- for review (or any science journal for that matter), ously” and “recently” are excellent hints that a sentence take a step back and ask yourself the following ques- may be written in the past tense! tions: • Are the verbs clear and recognizable? Tip 2: Queries • Will the reader have trouble understanding the The Cadmus editors may insert queries to ensure that we meaning of the text? have not altered the author’s meaning in any way. We are • Am I making my readers work too hard to not science experts, but we want to be sure the information understand the concepts in the article? is presented in a clear, easily understandable manner. As an • Have I been consistent throughout the text author, please be sure to answer all queries in the manu- when using abbreviations, hyphens, and script, even to approve a change that the editor has made. capitalization?

December 2008 ASBMB Today 19 2009 annual meeting The 2009 Fritz Lipmann Lectureship: Douglas C. Rees

ouglas C. Rees, a Howard Hughes Medical Institute the protein that imports vitamin B12 into Escherichia coli, Dinvestigator and professor of Chemistry at the Cali- would be appropriate for his structural studies. Rees and fornia Institute of Technology, will give the Fritz Lipmann his colleagues were able to produce crystals of the trans- Lectureship at the 2009 ASBMB Annual meeting. This porter and solve its structure. Based on their results, they lectureship recognizes investigators who make conceptual proposed a model for the transporter’s molecule pumping advances in biochemistry, bioenergetics, and molecu- ability. This initial structure also enabled them to crystal- lar biology. Rees will present his award lecture in New lize and solve the structure of the intact, nucleotide-free Orleans on Sunday, Apr. 19 at 8:30 a.m. HI1470/1 transporter from Haemophilus influenza, a Rees has been an HHMI investigator since 1997 and is member of the family of binding protein-dependent bacte- the Roscoe Gilkey Dickinson professor of Chemistry at rial ABC transporters that mediate the uptake of metal- the California Institute of Technology as well as an adjunct chelate species, including heme and vitamin B12. professor of Physiology at the University of California, Los Since solving these structures, Rees has added many Angeles, School of Medicine. He received his B.S. degree other projects to his repertoire, including: in Molecular Biophysics and Biochemistry from Yale Uni- • Nitrogenase: The biological conversion of dinitrogen versity in 1974 and his Ph.D. in Biophysics from Harvard to ammonia is catalyzed by the nitrogenase enzyme University in 1980, working with William Lipscomb. From system, which consists of two component proteins, 1980 to 1981, he was a postdoctoral fellow at Harvard the iron (Fe-) protein and the molybdenum-iron and from 1981 to 1982, he was a postdoctoral fellow at (MoFe-) protein. Rees and his colleagues have the University of Minnesota with James Howard. He then determined the structures of both proteins and joined the faculty at the University of California, Los their metal centers and are currently developing Angeles before moving to Caltech in 1989. mechanistic models for the nitrogenase reaction. Rees has made pivotal contributions to understanding • Extremely Thermostable Metalloproteins: Rees the structure of integral membrane proteins, membrane determined structures of the tungsten-containing transport mechanisms, and metalloenzyme structure and aldehyde ferredoxin oxidoreductase and a rubredoxin mechanism. His research focuses on structural bioenerget- from Pyrococcus furiosus, an archaeon that grows ics, which is the description of biological energy trans- optimally at 100° C. He is now using these structures duction processes at a molecular level. One of his group’s to identify the origins of the proteins’ thermostability. major goals is to characterize the structures and mecha- • Membrane Proteins: Structural and sequence nisms of ATP-dependent transduction systems, including analyses of membrane proteins indicate that the membrane proteins that catalyze energy transduction same general structural and energetic considerations processes associated with transport, mechanosensation, govern the three-dimensional structures of both and respiration-linked electron transfer reactions. water-soluble and membrane proteins. Currently, Rees’ graduate training was in x-ray crystallography, Rees and his colleagues are looking at the and while studying as a postdoctoral fellow at Minnesota, structures of succinate quinone oxidoreductase he became interested in how ATP and other large mol- and photosynthetic reaction centers to assess the ecules are used for energy in the body. One way in which generality of this conclusion and to establish the organisms harness this energy is via ATP binding cassette structural organization of the redox centers. (ABC) transporters, which use the binding and hydrolysis • Fibroblast Growth Factors (FGF): These proteins of ATP to pump molecules against concentration gradients stimulate the growth and development of many across cell membranes. When Rees started as an indepen- different cell types. Rees has solved the structures dent investigator, no structure of an ABC transporter had of two members of the FGF family and recently been determined. Rees surveyed several ABC transporters determined how the anti-ulcer drug, sucrose from a variety of organisms before deciding that BtuCD, octasulfate, and heparin fragments bind to FGF.

20 ASBMB Today December 2008 2009 annual meeting The 2009 ASBMB Merck Award: John Kuriyan

ohn Kuriyan, Howard Hughes Medical Institute signaling and solved the structure of the auto-inhibited Jinvestigator and Chancellor’s professor at the Univer- Src-family cytoplasmic tyrosine kinase (Hck). This structure sity of California, Berkeley will be honored with the 2009 explained nearly a century of research on the oncogenic ASBMB Merck Award for his exceptional achievements in v-Src gene and its normal counterpart. Kuriyan has also and contributions to structural biology. Kuriyan is one of shown how the signaling pathways that operate downstream the world’s leading researchers on the structure and func- of tyrosine kinases are controlled, solving the structures of tion of protein kinases, and his studies of c-Src, c-Abl, and a signal transducer and activator of transcription (STAT) Ca2+/calmodulin-dependent protein kinase (CaMKII) have factor and the nucleotide exchange factor that activates Ras, provided exciting new insights into the structure and func- Son-of-Sevenless (SOS), bound to Ras. He also solved the tion of molecular systems that are similar to those found in structure of the Abl tyrosine kinase catalytic domain bound many other biological contexts. He will present his award to the small molecule inhibitor STI571 (Gleevec), showing lecture at the ASBMB annual meeting in New Orleans on how the drug selectively inhibits the kinase. More recently, Tuesday, Apr. 21 at 8:30 a.m. Kyrian has determined the structure of auto-inhibited ZAP- Kuriyan received his B.S. in Chemistry from Juniata Col- 70, a tyrosine kinase that plays a critical role in T-cell activa- lege in Huntingdon, Pennsylvania before attending gradu- tion and has determined the auto-inhibitory mechanism of ate school at the Massachusetts Institute of Technology. CaMK-II. Working as a computational chemist with mentors Gregory In an entirely separate line of research, Kuriyan’s labora- A. Petsko (MIT) and (Harvard Univer- tory has made pioneering discoveries in the field of proces- sity), he received his Ph.D. in Physical Chemistry in 1986 sive DNA replication, most notably by determining the with a thesis titled “The Structure and Flexibility of Myo- structure of the sliding clamp of E. coli DNA polymerase III, globin: Molecular Dynamics and X-ray Crystallography.” which established the principle that chromosomal replicases After graduating, Kuriyan became a postdoctoral fellow at achieve high processivity by utilizing a circular “sliding , continuing his work with Karplus and clamp” protein that provides a mobile tether on DNA. This Petsko. was followed by the determination of the structures of In 1987, Kuriyan became an assistant professor at Rock- the clamp loader complexes from E. coli and . Most efeller University and climbed up the ranks to eventually recently, his laboratory has determined the first structure of become the Patrick E. and Beatrice M. Haggerty Professor the catalytic subunit of a bacterial DNA polymerase, result- and Associate Dean of Graduate Studies at Rockefeller. In ing in the discovery that the prokaryotic DNA polymerases 2001, he left Rockefeller to become divisional deputy for are related in structure to nucleotidyl transferases rather structural biology at the Advanced Light Source Physical than eukaryotic DNA polymerases, providing support for Biosciences Division at the Lawrence Berkeley National the idea that DNA replication may have arisen indepen- Laboratory, as well as Chancellor’s professor of molecular dently in the major branches of life. and cell biology and chemistry at the University of Califor- “John is arguably the preeminent structural biologist nia, Berkeley. In 2007, Kuriyan was promoted to head of of his generation,” says Tony Hunter of the Salk Institute. the Division of Biochemistry and Molecular Biology in the “Through his elegant crystallographic and modeling studies, Department of Cell and Molecular Biology at Berkeley. John has made truly seminal contributions to our under- Kuriyan has made several major contributions to the standing of how signals are transduced in mammalian cells area of cell signaling, starting with his determination of the and how DNA replication processivity is achieved in both first crystal structure of an Src homology 2 (SH2) domain bacterial and mammalian cells. John’s structural work and bound to a tyrosine-phosphorylated peptide. This led to his biochemical follow-up is characterized by its elegance and explanation for the sequence-specific recognition of phos- clarity of thought. He selects important problems that will photyrosyl peptides by SH2 domains. Kuriyan then decided be illuminated by structural insights and seems to come up to look at multi-domain proteins involved in tyrosine kinase with an exciting new principle each time.”

December 2008 ASBMB Today 21 2009annualmeeting continued The 2009 FASEB Excellence in Science Award: Susan Lindquist

he 2009 FASEB Excellence in Science Award will believes that the self-perpetuating folding of its Tbe presented to Susan Lindquist, a Howard Hughes domain acts as a molecular memory. She is currently Medical Institute Investigator and Professor of Biology at attempting to identify the structural core of the CPEB Massachusetts Institute of Technology (MIT). The award, amyloid and to pinpoint regions involved in nucleating which is sponsored by Eli Lilly and Company, recognizes prion formation. women whose outstanding career achievements in bio- Lindquist’s laboratory also focuses on the molecu- logical science have contributed significantly to further lar chaperone (heat-shock protein 90), which our understanding of a particular discipline by excellence promotes the maturation of signal transducers, pro- in research. Lindquist will receive her award and present teins regulating a multitude of processes controlling an award lecture at the ASBMB annual meeting in New life, death, growth, and development. Lindquist found Orleans on Tuesday, Apr. 21 at 2:10 p.m. that Hsp90 buffers the effects of a multitude of silent Lindquist received her undergraduate degree in polymorphisms at normal temperatures in Drosophila microbiology from the University of Illinois and her melanogaster, but when the organism is stressed, the Ph.D. in Biology from Harvard University in 1976. After effects of these polymorphisms are exposed. Selection a postdoctoral fellowship at the University of can then act on the traits these polymorphisms pro- she became an Assistant Professor of Biology at the duce. Lindquist hypothesizes that Hsp90 is a capacitor . She was promoted to Associate for morphogenetic evolution, allowing organisms to Professor of Biology in 1984, became a full professor accumulate that remain silent under optimal in 1988, and was named the Albert D. Lasker Profes- conditions and releasing their effects during stress when sor of Medical Sciences in 1999. In 2001, she became they might provide a survival advantage. the director of the for Biomedical Linquist and her colleagues are also using yeast mod- Research. She held that position until 2004 and remains els to investigate neurodegenerative diseases that have a member of the Whitehead Institute today. been linked to protein misfolding and the accumulation Work in Lindquist’s laboratory covers a broad range of of protein aggregates such as Parkinson and Hunting- topics unified by one theme, the protein-folding problem. ton disease. Using a yeast model of Parkinson disease She and her colleagues have used a variety of organisms expressing inducibly toxic levels of human α-synuclein, and techniques to investigate different aspects of protein they performed high-throughput chemical, genetic, and folding including folding mechanisms, impediments cyclic peptide screens for modifiers of toxicity. In this to correct folding, and consequences of misfolding on study, Linquist and her colleagues discovered that sev- biological systems. eral of these modifiers could specifically reverse toxicity One of the areas Lindquist studies is prion assembly in neuronal cell cultures and animal models of Parkin- and inheritance. propagate via conversion of one son disease. They are also using a model of Huntington domain of the protein into an amyloid fold. This conver- disease to screen for chemical and genetic modifiers sion occurs through a molten oligomeric intermedi- and are generating additional yeast models of protein- ate. Lindquist and her colleagues have identified the folding diseases as well. Their results suggest that the critical nucleating contacts involved in the conversion approach of expressing a toxic human disease protein in of the yeast prion protein Sup35. Using peptide arrays, yeast will be broadly applicable to a range of neurode- they determined that the intermolecular contact region generative diseases. controls the species specificity of protein interactions Lindquist has also found that eliminating HSF1, the (and hence the species barrier) and also the formation dominant regulator of the heat-shock response, pro- of distinct prion strains. Lindquist and her colleagues tects mice from tumors induced by oncogene muta- have also discovered that a regulatory protein that plays tions. Ironically, activation of the heat-shock response an important role in synaptic plasticity, cytoplasmic is a double-edged sword in the prevention of deadly polyadenylation element-binding protein (CPEB), also diseases; although it can prevent the protein aggregation behaves as a prion in yeast. CPEB maintains synapses associated with degenerative diseases of aging, it also by promoting the local translation of mRNAs. Lindquist puts tissues at risk for cancer.

22 ASBMB Today December 2008 educationfirstsecond and words training ASBMB Targets Secondary Education BY ELLIS BELL

romoting the molecular life sciences at the K-12 To apply to be a mentor for this program, UAN Plevel has always been a priority for ASBMB. In the faculty should submit the following materials by Feb. coming months, the society will initiate two new pro- 1, 2009: grams that target middle and high school science. • The name of a grade 7-12 teacher and a letter from The first is an awards program for middle and high the teacher indicating interest in participating in school science fairs in which ASBMB will offer prizes and the program. recognition for biochemistry- and molecular biology- • Evidence of support for summer undergraduate related projects. The awards will be administered by local student(s). This could be institutional or grant chapters of the Undergraduate Affiliate Network (UAN). support—no support for summer undergraduate If you are a UAN Faculty Advisor and would like to get students is provided by ASBMB. involved in sponsoring science fair awards in your area, • A brief overview of research that will be conducted. you can get details from your UAN Regional Director. • Plans for year-round involvement of faculty and The second initiative is a grade 7-12 teachers’ sum- undergraduates with the grade 7-12 teacher and mer research program. This new program, which will their class during the school year, including plans run for two years on a trial basis, will pair grades 7-12 for science fair activities. teachers and students with UAN faculty mentors and • Plans for assessment of outcomes in terms of undergraduates for a two-summer research experience. impact of both the grade 7-12 classroom and the Through this program, we hope to promote research- undergraduate students. based educational activities by building connections The above materials should be discussed with a UAN between teachers and students in secondary schools and Regional Director before submission. Final materials colleges. Moreover, we hope the program will present should be sent electronically to the appropriate UAN grades 7-12 students with role models and provide UAN Regional Director. Email address and contact infor- faculty and their students with meaningful service- mation can be found on the Undergraduate Affiliates learning opportunities. Network website (tinyurl.com/5vkt68). In the pilot program, we will pair one grade 7-12 The UAN faculty mentor will be expected to sub- school teacher and student with a UAN faculty men- mit both an interim and final report. The second year tor and student in each of our UAN regions. The teams of funding depends upon successful submission and will work together for two years (two summers and one review of the interim report. academic year) to: The whole team (secondary and undergraduate • Conduct scientific research for a minimum of four teacher, faculty, and students) will be invited to partici- weeks each summer. pate in the ASBMB Small Education Meeting in early • Develop a classroom activity or a science museum August 2009 to discuss what worked and what problems activity related to the research. were encountered. As part of that meeting, the teacher • Develop a multimedia tie-in with the State Standards and faculty member will attend an assessment and grant of Learning guides. writing workshop. • Develop a multimedia vignette of a career involving The UAN faculty member will also be encouraged to science aimed at K-12 students. submit an abstract describing his or her program and its • Maintain contact throughout the year via classroom outcomes at subsequent ASBMB annual meetings. visits by the undergraduate faculty and students, science fair activities, etc. Ellis Bell is currently Professor of Chemistry and Chair of the Each summer, the secondary school teachers will Biochemistry & Molecular Biology Program at the University receive a $4,000 award, and the students will receive of Richmond. He is also Chair of the ASBMB Education and $1,000. The UAN faculty mentors will also receive $200 Professional Development Committee. He can be reached at in support. [email protected].

December 2008 ASBMB Today 23 educationandtraining continued Minnesota State University Moorehead UAN Chapter Hosts Regional Science Meeting BY JOSEPH PROVOST

n Friday, Oct. 17 and Saturday, Oct. 18, the UAN Students also participated in an oral and poster competition. Ochapter from Minnesota State University Moorhead The winners of $400 Travel Awards to attend the ASBMB (MSUM) and Concordia College hosted the fourth annual annual meeting in New Orleans were: Undergraduate Research in the Molecular Sciences (URMS) • Alex Ritter (Concordia College), meeting. This meeting was attended by over 90 students • Jarrett Failing (North Dakota State University), and faculty from 12 different schools in Minnesota, North • Andrew Haak (Minnesota State University Moorhead), Dakota, and South Dakota. and Thomas Murray, Professor and Chair of the Department • Craig Kutz (Minnesota State University Moorhead). of Pharmacology at Creighton University School of Medi- cine in Omaha, presented his work on “Neuroactive Drugs Honorable Mentions were awarded to: from the Sea.” • Micheal Scheidt (Concordia College), Students presented their research both orally and in • Jenny Canine (Minnesota State University Moorhead), poster sessions and were treated to a seminar on biochem- • Shandon Collins (Minnesota State University istry and microbiology in the beef processing industry by Moorhead), Don Morrow from Creekstone Farms. • Dan Fetzer (Minnesota State University Moorhead), A break-out session on how to get into medical school • Nichol Haverland (Minnesota State University was given by Judy Demers, Chief Admissions Officer at Moorhead), the University of North Dakota School of Medicine. Other • Peace Enuh (Concordia College), break-out sessions included how to get into grad school (by • Megan Getting(University of North Dakota), and Murray), how to get a job in industry, and starting, sustain- • Danielle Rastadt (Minnesota State University ing, and funding undergraduate research. Moorhead).

Joseph Provost is Chair of the Biochemistry and Biotechnology Program Committee as well as Professor in the Department of Chemistry at Minnesota State University Moorhead.

Travel Award Winners

URMS Attendees

24 ASBMB Today December 2008 educationandtraining continued ASBMB 2008 Graduation Survey Results BY JAMES ZIMMERMAN

fter a three-year hiatus, the annual ASBMB gradu- while Spelman College deserves special notice for the Aation survey is back, and the results are encourag- number of awarded doctoral graduate degrees. ing. While only 220 of the 831 contacted departments The Biology and Biochemistry Department at the responded (about the same number as usual), the University of Houston was by far the leading producer number of undergraduates reported receiving bacca- of Hispanic baccalaureate degrees, and the Biological laureate degrees was up by more than 10 percent (the Sciences Department of Louisiana State University was highest ever reported in our survey), and the number the major producer of Hispanic Ph.D.’s. of doctorate degrees reported increased by almost 20 The Department of Chemistry and Biochemistry percent (the second highest ever reported). However, at Arizona State University led the way in graduating the number of master’s degrees reported was down over those identifying themselves as Pacific Islanders. 40 percent (the lowest ever reported). There has also been a change at the faculty level. Especially encouraging are the reports of tremendous While the average size of the tenured faculty reported increases in minority graduates at both the baccalaure- has not changed in the five years since the data was ate and doctoral levels. This year, more Native Ameri- last reported (15.8 percent in 2003 and 15.9 percent in can, Hispanic, and Black students received degrees than 2008), the percentage of women in these tenured posi- any other time in our nine previous surveys. tions has increased from 22 to 35 percent. Congratulations should go to the Department of A list of schools known to offer degrees in Biochem- Biochemistry, Biophysics & Molecular Biology at istry, Molecular Biology, Biotechnology, or Chemistry Whitman College, the Department of Biochemistry with a Biochemistry option can be found online at & Biophysics at Oregon State University at the under- www.asbmb.org/Page.aspx?id=1702. If your school graduate level, and to the University of Washington at offers such a degree and is not on the list, please contact the doctorate level for the number of Native Americans us at [email protected]. receiving degrees. These survey results can also be found online at The Biology & Biochemistry Department at the asbmb.org/Page.aspx?id=1702. University of Houston, the Chemistry Department at Spelman College, and the Department of Chemistry at James Zimmerman is an Emeritus Professor of Biochemistry at Tennessee State University deserve special notice for Clemson University and is a Visiting Professor of Chemistry at the number of Black baccalaureate degrees awarded, Colby College.

Graduation Survey Results Female Male Female Male Female Male B.A./B.S. B.A./B.S. M.A./M.S. M.A./M.S. Ph.D. Ph.D. American Indian or Alaskan Native 22 23 1 1 10 8 Asian 296 282 20 16 51 53 Black, not of Hispanic Origin 91 59 8 5 12 14 Hispanic 84 59 11 5 16 25 Pacific Islander 12 8 3 0 1 2 White, not of Hispanic Origin 773 773 54 50 125 172 International Students 71 56 34 30 102 109 Unspecified 62 51 1 6 12 19 Total 1411 1311 132 113 329 402

December 2008 ASBMB Today 25 minorityaffairs Core of Diversity: NUCLEUS Celebrates 15 Years of Support to Under-represented Science Majors BY JACQUELINE ALDRIDGE, DAVID USHER, AND HAL WHITE

hinedu Nworu, a Cell Biology and Anatomy graduate participating in NUCLEUS initiatives are provided with Cstudent at the University of Arizona, doubts he would supplemental academic advising, monitoring, tutorial sup- be in graduate school now if it hadn’t been for NUCLEUS. port, academic and professional development workshops, Nicole Barkley, a graduate student in Biological Sciences at and peer and professional mentoring programs. These layers the University of Maryland Baltimore County, also praises of support help students realize their potential as future NUCLEUS for providing the support she needed at a scientists and cultivate their membership in a community of majority white institution. These sentiments are shared by scholars of like-minded individuals pursing similar aca- many undergraduates who have been nurtured and encour- demic and career pathways. aged by the University of Delaware’s NUCLEUS program Each year 100–150 students benefit from the NUCLEUS that celebrated its 15th anniversary this year. program. Currently, the program’s students are 57 percent African-American, 17 percent Latino, 16 percent Asian, Foundation and Focus 1 percent Pacific Islander, and 9 percent Caucasian. Sixty- Initiated as part of a Howard Hughes Medical Institute four percent of the participants are female, and 36 percent (HHMI) Undergraduate Science Education Grant, the are male. The average cumulative and semester grade point NUCLEUS program at the University of Delaware has average for the participants in 2007–08 was 3.05 (B average). served under-represented students in the sciences since During the Spring and Fall 2007 calendar year, 25 percent of 1993. The acronym is intended to be iconic for both biology NUCLEUS students attained Dean’s List status by earning a and chemistry students and stands for Network of Under- GPA of 3.3 or higher and were recognized for their academic graduate Collaborative Learning Experiences for Under- achievements at the annual Dean’s List Dinner in the spring. represented Scholars. NUCLEUS is designed to recruit, Now in its 16th year, the NUCLEUS program continues retain, and graduate academically talented African-Amer- to focus on recruiting and retaining under-represented ican, Latino, Native-American, and Asian students major- students in the sciences at the University of Delaware by ing in science disciplines. NUCLEUS seeks to increase the providing an array of academic enrichment activities that ethnic representation and cultural diversity in the sciences, serve as supplemental resources in fostering academic suc- while providing an environment that encourages academic cess. Particularly successful are seminar series that address achievement, leadership, and service. issues students commonly face as science students. Semi- Phillip Gottlieb conceived the program and hired Victoria nars entitled: “How to Thrive in the Sciences: How to Study Orner as the first NUCLEUS coordinator. The HHMI has in Groups, Preparing for Science Classes, and How to Talk continued to support the NUCLEUS program through three with Your Professors,” “Academic SWOT Analysis: Identify- additional grant cycles and subsequent coordinators ­Cherie ing Strengths, Weaknesses, Opportunities, and Threats as Dotson (1998–2005), Zakiya Wilson (2005–2006), and a Science Student”, and “Recommendation Letter Etiquette Jacqueline Aldridge (2006–present)—under the direction of and Personal Statement Workshops” are held to help stu- Hal White and David Usher. Each coordinator has provided dents improve study skills, techniques, and habits as well as a personal touch in encouraging and motivating students to their communication skills with faculty. achieve academic, professional, and personal excellence. Mentoring, Service, and Research Student Support and Enrichment Another significant feature of NUCLEUS is its Lasting The mission of the NUCLEUS program from the start has Links Peer Mentoring program. This program is led by been to provide multi-faceted support for students majoring selected students (NUCLEUS Student Program Coordina- in a variety of basic science and health disciplines. Students tors) who match freshmen and transfer students with older

26 ASBMB Today December 2008 minorityaffairs

College Research Fellows, 4 Biotech- nology Institute Fellows, 7 industrial interns at DuPont and AstraZeneca, 2 National Science Foundation Research Experiences for Undergraduate Scholars, and 3 HHMI EXROP Schol- ars. These students have presented their work at a variety of scientific meetings, some of which include the International Bone and Cancer Conference, the American Society of Androlology Conference, the Annual Biomedical Research Conference for Minority Students, and the ASBMB Annual Meetings. Most of the students participating in research have gone on to graduate or professional school.

Former NUCLEUS Coordinators Cherie Dotson (left) and Victoria Orner (right), with 15 Years and Counting the current coordinator, Jacqueline Aldridge (center) at the 15th anniversary NUCLEUS banquet. In April, over 125 students, NUCLEUS alumni, faculty, and parents gathered for a banquet to celebrate 15 years and veteran students who have been in the program. Peer of the NUCLEUS program. Among the attendees were mentoring goes beyond assistance with course work. It is former coordinators Victoria Orner, now Associate Direc- designed to foster a sense of “community scholars” among tor of Admissions, Saint Michael’s College, Colchester, VT, students who share common academic and career interests. Cherie Dotson, now Student Affairs Program Manager These activities, along with others, have proven to be effec- for Graduate Student Recruitment & Outreach for the tive in improving grade point averages as well as personal College of Pharmacy at the University of Michigan, and and professional qualities of students. featured speaker Marijka Grey, one of the early graduates To show NUCLEUS students that pursuing science and of the program, who reflected on her NUCLEUS experi- health care careers is highly relevant to themselves and their ences and shared the lessons she had learned in her career. communities, students have been encouraged to participate While maintaining its ties to the past, the NUCLEUS in health disparity outreach activities. Since the fall of 2007, program continues to focus on the future and is well poised students have been asked to select a health topic and partici- to continue its impact on diversity in science. As current pate in a variety of discussions and community activities NUCLEUS coordinator Jacqueline Aldridge states, “When related to the chosen topic. Students began this initiative students join NUCLEUS, they are met with a standard that by participating in the AIDS Walk, co-hosting a free HIV has already been set for them. I want students to understand testing and education event, and hosting a series of health that it’s not enough just to meet someone else’s standard, disparity discussions related to breast cancer, prostate can- but to accomplish your goals in life, you must meet the bar, cer, obesity, and HIV. surpass it, and set a new standard.” Finally, undergraduate research is one of the funda- mental components of a student’s academic experience Jacqueline Aldridge is NUCLEUS coordinator at the University at the University of Delaware. An increasing number of of Delaware; David Usher is an Associate Professor and NUCLEUS students have become involved in undergradu- Associate Chairperson in the Department of Biological Sciences ate research through its research apprentice initiative. at the University of Delaware; and Hal White is a professor in Since 2003, there have been 27 research apprentices, 34 the Department of Chemistry and Director of the University of HHMI Summer Scholars, 32 McNair Scholars, 1 UNCF Delaware’s Howard Hughes Medical Institute Undergraduate Merck Scholar, 1 Fogarty Research Fellow, 2 Imperial Science Education Program.

December 2008 ASBMB Today 27 biobits asbmb journal science

Going From Why Red Wine Is Skin to Islet Good for Your Brain Although islet cell transplantation has shown great Epidemiological studies have shown that, among promise for achieving insulin independence for other health benefits, moderate consumption of red patients with type I diabetes, the dearth of matched wine can decrease the incidence of Alzheimer dis- organ donors and the necessity for chronic immuno- ease (AD). The active compounds in wine that con- suppression makes this treatment less than ideal for tribute to this benefit are most likely polyphenols, and the general diabetes population. Therefore, signifi- in this study, the cant research efforts have been put into deriving islet researchers de- cells from stem cell populations, such as this study, scribe the effects in which the researchers build upon the recent work of one such grape in successfully reprogramming human skin cells to seed polyphenolic resemble stem cells. They found that these induced extract (GPSE) on pluripotent stem (iPS) cells can differentiate into islet- the assembly and like clusters that contain cells positive for pancreatic dynamics of amy- biomarkers glucagon and C-peptide. Importantly, loid β-proteins, these clusters have the major culprits in

capability to respond to AD pathogenesis. Structure of MegaNatural-AZ, a grape glucose treatment with Using a combina- seed polyphenol that may protect against Alzheimer disease. insulin secretion. The tion of approaches researchers point out that including CD the efficiency of generat- spectroscopy and photo-induced cross-linking, they ing functional islet-like found that this commercially available extract, called clusters still needs to MegaNatural-AZ (MN), was a potent inhibitor of all be improved, and the stages of amyloid formation: protofibril formation, safety issues associated peptide oligomerization, and assembly into amyloid with iPS cells must be β-sheet aggregates. Cytotoxicity assays also dem- resolved before clinical onstrated that MN was cell-protective when mixed application, but this study in with amyloid proteins prior to either peptide does provide evidence assembly or addition of peptides to cells. Taken to- Islet-like cell clusters derived that insulin-producing gether with recent mouse studies showing that MN from human stem cells (top) or reprogrammed human cells might someday be can attenuate AD-like cognitive defects, this work skin cells (bottom) both easily generated from suggests that MN could be a potent therapeutic produce insulin by-product C-peptide (red) upon glucose skin in a patient-specific agent against AD. stimulation. manner.

Effects of Grape Seed-derived Polyphenols Generation of Insulin-secreting Islet-like on Amyloid β-Protein Self-assembly Clusters from Human Skin Fibroblasts and Cytotoxicity Keisuke Tateishi, Jin He, Olena Taranova, Kenjiro Ono, Margaret M. Condron, Lap Ho, Gaoyang Liang, Ana C. D’Alessio, and Jun Wang, Wei Zhao, Giulio M. Pasinetti, Yi Zhang and David B. Teplow J. Biol. Chem. 2008 283, 31601-31607 J. Biol. Chem. 2008 283, 32176-32187

28 ASBMB Today December 2008 biobits asbmb journal science For more ASBMB journal highlights go to www.asbmb.org/Interactive.aspx

Lipid Changes The Wonders of GFP During Fertilization Advances in high-throughput genetic screening have yielded large sets of potential protein-protein The fertilization of a sperm and an egg involves interactions that now need to be verified and further metabolic activation, membrane fusion events, and investigated. In this study, the researchers developed the production and hydrolysis of phospholipids. Until a simple assay to accomplish just that, combining now, though, there has been no thorough quantifica- the power of a yeast two-hybrid system with fluores- tion of the varied phospholipid changes during fer- cence imaging of GFP to directly visualize protein- tilization. In this study, researchers have combined protein interactions in living cells. This fluorescent traditional fatty acid analysis by thin-layer chro- two-hybrid (F2H) assay uses a modified lac repres- matography (TLC) and gas chromatography, along sor system to tether a fluorescent bait protein at a with a new measurement technique involving high chromosomal lac operator array, producing a brightly pressure liquid chromatography (HPLC) separation colored spot. Fusion prey proteins with a different and evaporative light-scattering detection to report fluorescence can then be assayed for co-localization, on lipid levels in eggs, sperm, and during fertilization as revealed by a change in color. With the F2H as- in Xenopus. Not surprisingly, sperm and eggs con- say, the researchers successfully investigated the tained significant differences in their phospholipid interaction of proteins from multiple subcellular content; for example, sperm contain more phos- compartments phatidylethanolamine but less phosphatidylcholine. including And, as expected, lipid composition changed dra- the nucleus, matically during cytoplasm, and fertilization as mitochondria. well, such as In combination a decrease with an S- in phosphati- phase marker, dylinositol likely they could also brought on by The F2H assay reveals the specific study the cell interaction of DNA Ligase III, but not the the increased cycle depen- homologous DNA Ligase I, with the DNA levels of PIP2. repair protein XRCC1. dence of these This detailed interactions. This study indicates that F2H could be examination A comparison of Xenopus egg (solid bar) a powerful tool to investigate protein-protein interac- and sperm (hatched bar) phospholipids. of the total tions within their cellular environment in real-time and amount and provides a fine example of what can be done with the composition of the major lipid classes during this recent awarding-winning GFP technology. developmental process should provide for a more comprehensive model of both gamete physiology and fertilization events. A Fluorescent Two-hybrid (F2H) Assay for Direct Visualization of Protein Interactions in Living Cells Lipid Levels in Sperm, Eggs, and Kourosh Zolghadr, Oliver Mortusewicz, During Fertilization in Xenopus Laevis Ulrich Rothbauer, Regina Kleinhans, Douglas W. Petcoff, William L. Holland, and Heike Goehler, Erich E. Wanker, Bradley J. Stith M. Cristina Cardoso, and Heinrich Leonhardt J. Lipid Res. 2008 49, 2365-2378 Mol. Cell. Proteomics 2008 7, 2279–2287

December 2008 ASBMB Today 29 sciencefocus Sung-Hou Kim: Consummate Crystallographer BY NICK ZAGORSKI

ymmetry. It’s a simple concept, mal organism and subsequently Syet whether they occur naturally “mapping” all known archi- or through man-made design, sym- tectural motifs in the protein metrical objects often evoke a sense of universe. beauty and wonder. But symmetry is more than just an aesthetically pleas- Opportunities and Luck ing design; it’s also an underpinning Unfortunately, though, while component of physics, chemistry, and the world of atoms and mol- biology. The symmetrical properties of ecules featured an abundance molecules define both their chemical of symmetry and balance, the and spectroscopic qualities and are a real world in South Korea was key reason the structures of proteins anything but when Kim was of crystallography in the entire U.S. “I and other macromolecules can be studying chemistry at Seoul National ended up being extremely well-trained deduced through x-ray crystallography. University in the late 1950s. In the in this field,” Kim notes. “In fact, in the These symmetrical properties are years since the end of the Korean War, last year of my graduate studies, I was also a major reason that Sung-Hou Kim’s homeland had been experiencing even helping other faculties with the Kim, professor in the Department a near-continuous period of political latest techniques in crystallography, of Chemistry at the University of and economic instability. “It was at the which was an unusual experience for a California, Berkeley, became enam- point where you really couldn’t plan foreign graduate student.” ored with science. Kim was a bit of a your life more than a few months in While completing his doctorate, in late-bloomer, as he was not interested advance,” Kim says, who, after complet- which he determined the structures in science until his final year of high ing his Masters in Chemistry in 1962, of small organic molecules like sugars school, when the beauty and func- realized that if he wanted to continue and sugar derivatives, which was tionality of molecular shapes led him his academic progress, it would be best considered very challenging because down a path of crystallography, a field to do so abroad. At the time, crystal- of the absence of heavy atoms, Kim in which symmetry was especially lography was popular in Europe, but became interested in the emerging field prominent. Kim preferred to find a place in the of “new biology,” referring to the birth And amongst the numerous U.S., as many of his friends had emi- of modern molecular biology in the scientists who have employed crystal- grated there. 1960s following the discoveries of DNA lography in their work, few have been Of the schools Kim applied to, the structure, gene expression, and the more prolific than Kim. He has been University of Pittsburgh was the first to genetic code. “So, I decided to switch dutifully solving molecular structures respond with an acceptance, which was over from chemistry to biology for for over 40 years, starting at a time enough for Kim to make his decision. my postdoc, even though most of my when using crystallography for protein It proved to be a good one, as he ended colleagues warned me not to do that, structures was not even feasible. Back up joining the lab of George Jeffrey, an because it was too big a change.” Kim then, he was content looking at the English crystallographer renowned for was steadfast, though, and when Jeffrey level of small molecules, but as his his work on hydrogen bonds, who had came to him one day and mentioned skills and vision matured, he moved up been recruited to Pittsburgh in 1953 that a colleague of his in the Massachu- the hierarchy; first looking at nucleic and had since set up one of the stron- setts Institute of Technology Biology acids, then proteins, and now, grand gest crystallography labs in the States; Department was looking for a postdoc, projects aimed at obtaining structural in fact, Jeffrey was responsible for Kim exclaimed, “I’ll take it,” before information of all proteins in a mini- creating the first graduate department even asking who it was.

30 ASBMB Today December 2008 sciencefocus

A Rich Endeavor to working with,” Kim says, “but for- proteins crystallize by the contacts The mystery professor turned out to be tunately Rich had enough confidence between hydrophobic surface patches, Alex Rich, who has become quite well- in my abilities that he let me try.” Kim thus making the charged and hydro- known for his work elucidating DNA notes this project got started partially philic surfaces of tRNAs non-crystal- and RNA structure. When Kim joined, from his ignorance of two well-known lizable. one of Rich’s lab projects was studying facts: one, several labs in Europe and This project took longer, but after abnormal base pairing, though this area the United States tried to crystallize five years of collaboration with skilled had been struggling due to an inability tRNAs without success—“Alex wisely colleagues of the structural group in to get structural data. “Alex knew I had did not tell me about this”­—and two, Rich’s lab (initially with Bud Suddath a strong crystallography background a prevailing wisdom then was that and Gary Quigley) and a little luck, and put me on the project,” Kim says, biological macromolecules such as Kim managed to solve the complete “and when I first looked at it, I knew I backbone structure of a tRNA, reveal- had been well-trained, because I said to ing its general shape for the first time. myself, ‘Okay, this should be easy.’” That work turned out to be a bigger Sometimes those can be famous deal than even Kim had imagined, last words, but Kim’s expertise as he quickly saw his work pop prevailed, and he solved the up on the front page of The problem in a short time, New York Times. “That was generating structures of so exciting,” he says, “and non-standard cytosine- it taught me not to be uracil and pheno- afraid to tackle some barbital (a uracil of the big problems of derivative)-adenine biology, and to take pairs. “And that ‘known’ facts and was great for me prevailing wisdoms because it gave with a grain of salt.” me a great deal of credibility in Proteins of the lab, which I Interest needed because After completing I wasn’t familiar his post-doctoral with this new training, Kim biology.” (Though moved on to a Kim made sure to professorship in attend numerous the biochemistry molecular biology department at lectures during his Duke University postdoc to learn as School of Medicine, much as possible.) where he continued That crystallo- his tRNA work with his graphic cachet helped own group (started with Kim tackle his next Jeol Sussman and George endeavor, which was Church) and, with the help determining the structure of a transfer RNA molecule, a hot Determining the L-shaped three- commodity in molecular biology dimentional structure of transfer RNA circles. “The size of the molecule was was one of Sung Hou Kim’s first major on a scale far beyond what I was used breakthroughs in the crystallographic arena.

December 2008 ASBMB Today 31 sciencefocus continued of his colleagues back at MIT, managed A global view of protein structure space. Kim has mapped 1,898 non-redundant protein structures in to piece together the complete atomic three-dimensions, revealing a sparsely populated structure. At Duke , recognizing the protein “cosmos” in which all of the known protein staggering diversity of proteins, he folds cluster mostly into four elongated regions, also took his first forays into protein which correspond to four classes: all-α, all-β, α+β, and α/β (indicated by red, yellow, purple, and cyan crystallography, initiating the structural spheres, respectively; small proteins and multidomain studies of a pair of recently discovered proteins are represented by green and black spheres, unusual proteins, monellin and thau- respectively). Reprinted from Choi, I.G. and Kim, S.-H. (2006) PNAS 103, 14056-14061. matin, that produced an intensely sweet sensation (over 1000 times more potent than sugar). In 1978, Kim relocated to Berkeley Protein Space, after being recruited by the a Final Frontier? school. “Initially, In the past decade, Kim has begun I wasn’t very keen taking a larger view of the world of pro- on the idea of teins. “When I first started my research, moving,” he says. not many people were doing structural “But I realized that biology,” he says. “But then, not long some of the proj- ago, I looked around me and saw all ects I was becoming these bright young people solving interested in required not complex protein structures, so I only a knowledge of biology, thought, ‘Okay, maybe I don’t have but also chemistry, physics, to do this anymore.’” and mathematics. I decided With that, Kim became one of the that Berkeley would give me a better first to enter the field of structural chance to interact with people of dif- genomics. “We had figured out how ferent backgrounds.” to solve large numbers of protein It wouldn’t take long for Kim to structures from hyperthermophiles interact with one such individual who quickly,” he says, “And I had an idea exposed him to new concepts. One that we could use these tools to get day, while he was working in his office, continued his penchant for structural global views of relative usage of archi- he was paid a visit by his Berkeley col- “firsts,” such as: first proto-oncogene tectural motifs (fold patterns) by pro- league Daniel Koshland, who started product (c-H-Ras) (in collaboration teins in one single organism and, then, explaining chemotaxis (Koshland’s with the groups of Susumu Nishimura in all organisms.” This idea, Kim notes, area of expertise) to a very intrigued and Eiko Ohtsuka), the first human arose after he heard about a project Kim. “I said, ‘Wow, that’s a really neat cyclin, CDK2 (in collaboration with in Lawrence Berkeley Lab aimed at system. How does the signal get from David Morgan’s group), and cyclin- creating a three-dimensional map of the outside to the inside of the cell?’ dependent kinase, and the first small the cosmic universe. His proposal, Koshland replied that he was unsure, . initially funded as a Department of because he had no idea what the The collaboration with Koshland Energy project, was taken up by NIH chemotaxis receptor looked like. So I also brought about a second major in 2000 as part of the Protein Structure said ‘Oh, really? Well, let’s get on it.’” epiphany for Kim. “Our structural Initiative (PSI). Get on it they did, and soon they data was actually not consistent with After accomplishing the first goal had solved the first structures of a some of the results Koshland’s group and obtaining protein fold informa- chemotaxis receptor, initially getting obtained through biochemistry,” he tion of over 92 percent of all soluble the external ligand binding domain says, “but now they could reinterpret proteins in the minimal organism and later the internal signaling their data based on the structure. Mycoplasma, Kim’s group developed domain, work which helped explain Right then, I realized how important a computational approach that took how weak chemotaxis signals can be structural information is, in order to about 2,000 unique protein structures readily amplified. Over the years, he unify all the other data about a bio- containing all the known architectural tackled other proteins of interest and logical molecule.” motifs and mapped them in space,

32 ASBMB Today December 2008 sciencefocus continued based on how closely related the folds of accurately comparing genome/chro- chromosomes is no easy feat—he’s were. “I had some thoughts as to how mosomal sequences.” As Kim listened equally impressed with how his home it would turn out, but much of my ini- to this talk, though, he wondered if country has grown since he left over tial intuition turned out to be wrong. he could modify this program for 40 years ago. Over the past several The results were full of surprises.” biology. If one considers each organ- years, he has taken numerous trips For one, Kim was confident that ism’s genome as a book and their DNA back to Korea, either to help set up the abundance and diversity of folds as the text—granted it’s text without new research institutes or act as an would fill up the protein fold space spaces, thus making each chromosome advisor for different governmental uniformly (like the cosmic universe) essentially one big word—then maybe offices, research and educational insti- as nature had billions of years to maxi- he could determine how much genetic tutes, “I can barely recognize it some- mize all the potential conformations. plagiarism two organisms share. times, even in contrast to as recently as However, the demography of protein “I’m convinced this method could 15 years ago.” structures concentrated in only four be a much more general way to Kim notes that the Korean govern- areas in the map, comprising alpha characterize species from bacteria to ment has been spending money on helices, beta sheets, a random mix of humans,” he notes. Of course, he will science and technology programs, the two, and an alternating alpha-beta tread carefully as evolution is not his and combined with an influx of bright mix (the most populated area); this specialty, but he’s tackled areas outside young scientists, many of whom mathematically derived demographic his expertise before and thinks an trained in the U.S. and have returned grouping ended up being remarkably outsider’s view sometimes can be very home, has spurred a new boom in similar to the Structural Classification revealing. research. “The only thing Korean System of Proteins (SCOP), based on For all the growth Kim has been research needs now is a stronger pres- visual comparisons. Kim could also doing as a scientist—going from the ence on the managerial level, getting use his model to figure out the age structures of simple sugars to entire in those scientists who have a good of certain motifs and found that the scientific vision and a practical sense alternating alpha/beta fold was the of how to realize the vision. But, I longest evolving protein family. think within the next generation, they Out of Focus: should be there.” Borrowing a Page Making a List, from the Plagiarists Checking It Twice… Nick Zagorski is a science writer for ASBMB. He can be reached at Encouraged by the mapping of the Picking the right graduate school [email protected]. protein structure universe, Kim is is always a challenge, and for currently excited about organizing the Sung-Hou Kim, who knew pre- whole genome/chromosome universe, cious little about American univer- REFERENCES Kim, S.-H., Quigley, G. J., Suddath, F. L., another project that stemmed from sities, it was a particularly big one. McPherson, A., Sneden, D., Kim, J. J., Weinzierl, an external lecture Kim listened in J., and Rich, A. (1973) Three-dimensional He admittedly had no idea which Structure of Yeast Phenylalanine Transfer RNA: on. This one came from the computer U.S. schools—if any—had strong Folding of the Polynucleotide Chain. Science 179, 285-288. science department, in a talk about crystallography programs, so he De Vos, A. M., Tong, L., Milburn, M. V., Matias, P. the computer programs used to detect M., Jancarik, J., Noguchi, S., Nishimura, S., decided the best bet was to let Miura, K., Ohtsuka, E., and Kim, S.-H. (1988) plagiarism in written texts (incidentally, the journals decide. “I just went to Three-dimensional Structure of an Oncogene Protein: Catalytic Domain of Human c-H-Ras these programs were originally devel- the library, picked out one of the p21. Science 239, 888-893; Correction: Science oped as a means to detect plagiarism (1989) 245, 244. current crystallography journals, Yeh, J. I., Biemann, H. P., Pandit, J., Koshland, D. in computer coding, as people would and made a short table ranking E., and Kim, S.-H. (1993) The Three-dimensional Structure of the Ligand-binding Domain of cheat by using someone else’s code, just universities by the number of pub- a Wild-type Bacterial Chemotaxis Receptor. Structural Comparison to the Cross-linked rearranged, in their own programs). lications they had.” When he was Mutant Forms and Conformational Changes “Normally, when scientists compare upon Ligand Binding. J. Biol. Chem. 268, 9787- done, he sent off his applications 9792. organisms, they pick a set of com- to the three most “prolific” institu- Kim, K. K., Yokota, H., and Kim, S.-H. (1999) Four-helical-bundle Structure of the Cytoplasmic mon genes and align them to examine tions on his list, which happened Domain of a Serine Chemotaxis Receptor. Nature similarity,” Kim says. “Now, depend- 400, 787-792. to be Pennsylvania State Univer- Hou, J., Jun, S.-R., Zhang, C., and Kim, S.-H. ing what genes you pick, you may get sity, the University of Pittsburgh, (2005) Global Mapping of the Protein Structure Space and Application in Structure-based different results. However, it’s still the and the University of Connecticut. Inference of Protein Function. Proc. Natl. Acad. only method because we have no way Sci. U. S. A. 102, 3651-3656.

December 2008 ASBMB Today 33 career opportunities

rience and a clear potential for, or demonstrated, excellence Missisippi State University in teaching, advising, research, service and/or grantsmanship. Assistant Professor Review of applicants will begin October 24, 2008, and will con- Department of Biochemistry tinue until a suitable candidate is identified. and Molecular Biology Applicants are required to complete the Mississippi State University (MSU) invites applications and nomi- Personal Data Information Form on-line at nations for the position of Assistant Professor with a cross-dis- www.jobs.msstate.edu. Please submit either ciplinary approach to the biochemical and/or molecular sciences on-line, at www.hrm.msstate.edu/employment/ with potential agricultural research applications consistent with postings.htm, or to the address below a letter of the mission of a Land Grant University in the Department of application outlining career goals, a curriculum Biochemistry and Molecular Biology. This 9-month tenure track vitae, transcripts and three letters of reference to: position has an anticipated 50% teaching and 50% research Scott T. Willard, Ph.D. appointment. The successful candidate will be expected to Department of Biochemistry develop a nationally recognized teaching and research program and Molecular Biology in their subject discipline, develop new and/or modify existing Box 9650 courses (including technology-based course development), pur- Mississippi State, MS 39762 sue extramural funds in support of research aims, and publish Email: [email protected], results in peer reviewed research journals. Applicants should telephone: 662-325-7736. have a Ph.D. in Biochemistry, Molecular Biology, or related field. Mississippi State University is an Affirmative Action/Equal Opportunity Preference will be given to candidates with postdoctoral expe- Employer.

             

                                                                                                                                                                                                                                                                     

                                             

34 ASBMB Today December 2008

scientific meeting calendar

The 22nd Biennial 2nd International DECEMBER 2008 Conference of the Australian Conference on Advanced & New Zealand Society Technologies & Treatments Exploring Modular for Mass Spectrometry for Diabetes (ATTD) Protein Architecture JANUARY 27–30, 2009 FEBRUARY 25–28, 2009 DECEMBER 3–5, 2008 SYDNEY, AUSTRALIA ATHENS, GREECE HEIDELBERG, GERMANY www.mmb.usyd.edu.au/ANZSMS22 www.2.kenes.com/attd/Pages/home.aspx www-db.embl.de/jss/EmblGroupsOrg/ conf_110 Biophysical Society February 2009 53rd Annual Meeting The Annual Meeting FEBRUARY 28–MARCH 4, 2009 of the American Society Gordon Research Conference— BOSTON, MA for Matrix Biology (ASMB) Plant Lipids: Structure, www.biophysics.org/2009meeting DECEMBER 7–11, 2008 Metabolism, & Function SAN DIEGO, CA FEBRUARY 1–6, 2009 www.asmb.net GALVESTON, TX MARCH 2009 www.grc.org/programs.aspx?year=2009 &program=plantlipid The 48th American Society for Deuel Lipid Conference Cell Biology Annual Meeting MARCH 3–6, 2009 BORREGO SPRINGS, CA DECEMBER 13–17, 2008 Molecular Targets for Cancer www.deuelconference.org SAN FRANCISCO, CA Prevention Conference www.ascb.org/meetings FEBRUARY 4–5, 2009 BETHESDA, MD Gordon Conference on http://web.ncifcrf.gov/events/ Oxidative Stress & Disease The Science of Eliminating cancerprevention/2009/default.asp MARCH 8–13, 2009 Health Disparities TUSCANY, ITALY DECEMBER 16–18, 2008 www.grc.org/programs. NATIONAL HARBOR, MD The 14th Annual aspx?year=2009&program=oxidat www.blsmeetings.net/2008healthdisparitie Proteomics Symposium ssummit/ FEBRUARY 6–8, 2009 LORNE, AUSTRALIA ACS Spring National www.australasianproteomics.org Meeting & Exposition MARCH 22–26, 2009 JaNUARY 2009 SALT LAKE CITY, UT Pacific Lipid Association www.acs.org/meetings Gordon Research 3rd Annual Scientific Forum Conference: Glycobiology FEBRUARY 20–22, 2009 JANUARY 18–23, 2009 SALT LAKE CITY, UT APRIL 2009 VENTURA, CA www.lipid.org www.grc.org/programs.aspx?year= 3rd International Congress 2009&program=glycobio on Prediabetes and the US HUPO 5th Annual Metabolic Syndrome— Conference Epidemiology, Management, Keystone Symposium– FEBRUARY 22–25, 2009 and Prevention of Diabetes Obesity: Novel Aspects of SAN DIEGO, CA and Cardiovascular Disease the Regulation of Body Weight www.ushupo.org APRIL 1–4, 2009 JANUARY 20–25, 2009 E-mail: [email protected] NICE, FRANCE BANFF, ALBERTA, CANADA Tel.: 505-989-4876 www.kenes.com/prediabetes www.keystonesymposia.org/Meetings/ ViewMeetings.cfm?MeetingID=997 ASBMB Annual Meeting Keystone Symposium– APRIL 18–22, 2009 Complications of NEW ORLEANS, LA Sanibel Conference Diabetes and Obesity on Mass Spectrometry: www.asbmb.org/meetings.aspx FEBRUARY 24–MARCH 1, 2009 Lipidomics and Lipids VANCOUVER, BRITISH COLUMBIA in Mass Spectrometry www.keystonesymposia.org/Meetings/ JANUARY 23–26, 2009 ViewMeetings.cfm?MeetingID=998 ST. PETERSBURG BEACH, FL www.asms.org/Default.aspx?tabid=70

36 ASBMB Today December 2008 scientific meeting calendar

Keystone Symposium— 3rd EuPA Meeting— Complex Lipids in Clinical Proteomics AUGUST 2009 Biology: Signaling, June 14–17, 2009 Compartmentalization, Stockholm, Sweden ACS Fall 2009 National and Disease www.lakemedelsakademin.se/templates/ Meeting & Exposition APRIL 22–27, 2009 LMAstandard.aspx?id=2529 AUGUST 16–20, 2009 OLYMPIC VALLEY, CA WASHINGTON, D.C. www.acs.org/meetings www.keystonesymposia.org/Meetings/ ViewMeetings.cfm?MeetingID=961 VII European Symposium of the Protein Society JUNE 14–18, 2009 18th International Mass Spectrometry Conference Arteriosclerosis, Thrombosis, ZURICH, SWITZERLAND www.proteinsociety.org AUGUST 30–SEPTEMBER 4, 2009 and Vascular Biology Annual BREMEN, GERMANY Conference www.imsc-bremen-2009.de APRIL 29–MAY 1, 2009 XV International WASHINGTON, D.C. www.americanheart.org/presenter. Symposium on jhtml?identifier=3057022 Atherosclerosis SEPTEMBER 2009 JUNE 14–18, 2009 BOSTON, MA World Congress on Oils and 2009 NLA Scientific Sessions www.isa2009.org Fats and 28th ISF Congress APRIL 30–MAY 3, 2009 SEPTEMBER 27–30, 2009 MIAMI, FL SYDNEY, AUSTRALIA www.lipid.org Gordon Research Conference: www.isfsydney2009.com Atherosclerosis JUNE 21–26, 2009 TILTON, NH MAY 2009 www.grc.org/programs. OCTOBER 2009 aspx?year=2009&program=athero 57th ASMS Conference 3rd ESF Functional Genomics on Mass Spectrometry Conference MAY 31–JUNE 4, 2009 SEB at Glasgow 2009 OCTOBER 1–4, 2009 PHILADELPHIA, PA JUNE 28–JULY 1, 2009 INNSBRUCK, AUSTRIA www.asms.org GLASGOW, SCOTLAND www.esffg2008.org E-mail: [email protected] www.sebiology.org/meetings/Glasgow/ Tel.: 505-989-4517 glasgow.html Bioactive Lipids in Cancer, Inflammation, JUNE 2009 JULY 2009 and Related Diseases (11th International VIII European Symposium Gordon Research Conference) of the Protein Society Conference: Molecular & OCTOBER 25–28, 2009 JUNE 7–11, 2009 CANCUN, MEXICO Cellular Biology of Lipids www.bioactivelipidsconf.wayne.edu ZURICH, SWITZERLAND JULY 19–24, 2009 Organizer: Andreas Plückthun WATERVILLE VALLEY, NH (University of Zurich) www.grc.org/programs. www.proteinsociety.org aspx?year=2009&program=lipids APRIL 2010

21st American Peptide 23rd Annual Symposium ASBMB Annual Meeting Society Symposium of the Protein Society APRIL 24–28, 2010 JUNE 7–12, 2009 JULY 25–29, 2009 Anaheim, CA BLOOMINGTON, IN BOSTON, MA www.asbmb.org/meetings.aspx www.21staps.org www.proteinsociety.org

Cancer Proteomics 2009 Protein Lipidation, AUGUST 2010 JUNE 8–12, 2009 Signaling, and DUBLIN, IRELAND Membrane Domains www.selectbiosciencies.com/conferences/ 14th International JULY 26–31, 2009 Congress of Immunology files/Agendas2009/CP2009_Agenda.pdf SAXTONS RIVER, VT AUGUST 22–27, 2010 src.faseb.org KOBE, JAPAN www.ici2010.org